Section 2 Electrospinning

**31**

**Chapter 2**

**Abstract**

Delivery

made drug release carriers.

tions are extensively profitable [1].

oral drug delivery

**1. Introduction**

Electrospinning and Drug

*Marilena Vlachou, Angeliki Siamidi and Sotiria Kyriakou*

**Keywords:** nanofibers, electrospinning, electrospinning parameters, polymers,

During the last years, nanofibers have become increasingly attractive as drug delivery systems, mainly because they enhance the delivery of limited absorption drugs by improving the dissolution rates and solubility of drug molecules. Moreover, nanofibrous approaches in preparing stable amorphous drug formula-

The principal methods used for the fabrication of polymer nanofibers include drawing, template synthesis, phase separation, self-assembly, solvent casting, and electrospinning. However, the latter has become the most frequently used technique because of its ability to afford nanofibers with unique characteristics. These include a very high surface area to volume ratio, a high porosity with a small pore size, improved mechanical properties, degradability, and flexibility in surface functionalities/motifs. All the other fabrication methods have limitations, with respect to the materials used, and moreover, they are laborious and complex processes, resulting in problematic scale-up. Furthermore, compared with the other processing techniques, electrospinning is a simple, user-friendly, reproducible, and continuous

A detailed account of the construction, properties, and practical applications of electrospinning for the fabrication of high-quality ultrafine fibers, suitable for drug delivery, is given. With respect to the electrospinning method, various parameters are of crucial importance. The electrospinning parameters are classified as solution properties, process parameters, and environmental conditions. The solution properties include the polymer concentration, molecular weight and viscosity, the solution conductivity and relative volatility, volatility of the solvent, surface tension, and dielectric constant. The process parameters refer to the flow rate, the applied voltage, the needle diameter, and the distance between the tip of the needle and collector and the geometry of the collector. The environmental conditions include the relative humidity and temperature. All these factors are responsible for a flawless electrospinning process, which leads to the formation of the desirable electrospun nanofibers with the requisite characteristics. In this chapter, it has been shown that the electrospinning technology could provide a useful method for modifying drug release behavior and opens new routes for the development of effective and tailor-

#### **Chapter 2**

## Electrospinning and Drug Delivery

*Marilena Vlachou, Angeliki Siamidi and Sotiria Kyriakou*

#### **Abstract**

A detailed account of the construction, properties, and practical applications of electrospinning for the fabrication of high-quality ultrafine fibers, suitable for drug delivery, is given. With respect to the electrospinning method, various parameters are of crucial importance. The electrospinning parameters are classified as solution properties, process parameters, and environmental conditions. The solution properties include the polymer concentration, molecular weight and viscosity, the solution conductivity and relative volatility, volatility of the solvent, surface tension, and dielectric constant. The process parameters refer to the flow rate, the applied voltage, the needle diameter, and the distance between the tip of the needle and collector and the geometry of the collector. The environmental conditions include the relative humidity and temperature. All these factors are responsible for a flawless electrospinning process, which leads to the formation of the desirable electrospun nanofibers with the requisite characteristics. In this chapter, it has been shown that the electrospinning technology could provide a useful method for modifying drug release behavior and opens new routes for the development of effective and tailormade drug release carriers.

**Keywords:** nanofibers, electrospinning, electrospinning parameters, polymers, oral drug delivery

#### **1. Introduction**

During the last years, nanofibers have become increasingly attractive as drug delivery systems, mainly because they enhance the delivery of limited absorption drugs by improving the dissolution rates and solubility of drug molecules. Moreover, nanofibrous approaches in preparing stable amorphous drug formulations are extensively profitable [1].

The principal methods used for the fabrication of polymer nanofibers include drawing, template synthesis, phase separation, self-assembly, solvent casting, and electrospinning. However, the latter has become the most frequently used technique because of its ability to afford nanofibers with unique characteristics. These include a very high surface area to volume ratio, a high porosity with a small pore size, improved mechanical properties, degradability, and flexibility in surface functionalities/motifs. All the other fabrication methods have limitations, with respect to the materials used, and moreover, they are laborious and complex processes, resulting in problematic scale-up. Furthermore, compared with the other processing techniques, electrospinning is a simple, user-friendly, reproducible, and continuous process [1–4], and upon the appropriate selection of the electrospinning apparatus and materials, diverse types of fibers, such as core-sheath, porous or hollow structured nanofibers can be produced.

### **2. Electrospinning**

As already mentioned, electrospinning is a simple, highly versatile and robust technique for the production of polymers and a wide range of materials, including ceramic, metallic, and long fibers with diameters from submicron down to nanometer scale. These fibers are produced by feeding a polymer solution, dispersion or melt in a high electric field. It is worth mentioning that the use of melt in the electrospinning process is costly and leads to more difficult production than using polymer solution [1–6].

#### **2.1 Electrospinning equipment**

The main setup of an electrospinning equipment involves three main parts all enclosed within a chamber. A typical electrospinning apparatus is shown in **Figure 1**. It is composed of an electrical supply, for generating a high-voltage power supply, a piece of feeding equipment, which consists of a glass syringe with metallic needle filled with the polymer solution, a pump suitable for controlling the flow rate of the polymer solution, and a grounded collector usually made from aluminum foil. The power supply is used to apply tens of kilovolt to the needle, which works as a spinneret, while the pump extrudes the polymer from the syringe to the collector, which can be either rotatable or static [2, 4, 5, 7–9].

#### **2.2 Electrospinning process and methods**

#### *2.2.1 Electrospinning process*

The working principle of electrospinning is straightforward: at ambient temperature, a polymer solution or melt is ejected from the tip of a needle to a grounded metal collector by applying high voltage between the needle and the collector [2]. In

**33**

*Electrospinning and Drug Delivery*

internal bulk content [1, 4, 11, 12].

loaded with all of these methods [3, 13, 14].

*2.2.2.1 Blending electrospinning*

*2.2.2 Electrospinning methods*

*DOI: http://dx.doi.org/10.5772/intechopen.86181*

detail, the electrospinning process starts with the application of high voltage, which creates electric charges that are moving toward the polymer solution in the syringe *via* the metallic needle. The induction of charges on the polymer droplet causes instability within the polymer solution, thus creating an electrically charged jet of polymer solution or melt. Concurrently, a force that opposes the surface tension is produced, by the mutual repulsion of charges, and as a result, the polymer solution flows in the direction of the electric field and is extruded from the needle of the syringe with the aid of a pump [4]. Specifically, the solution jet is ejected from the nozzle of the needle when the voltage exceeds a threshold value because the electric force overcomes the surface tension of the droplet. Each droplet is exposed to a high voltage, and a cone-shaped droplet is formed. This is known as the Taylor cone and is caused due to the electrical voltage, which is the difference voltage between the nozzle and the collector with the counter charge [8]. Subsequently, the charged jet of solution is evaporated or solidified before reaching the metallic collector, where the solid material is collected as a solid interconnected continuous network of small fibers [1, 8, 10]. Regarding the electrospinning process, a stable charge jet can be formed only if the polymer solution has adequate cohesive force. During the process, the internal and external charge forces cause the whipping of the liquid jet, thus permitting the polymer chains to stretch and slide into the solution pushing the jet toward the collector [4]. As a result, the created fibers have enough small diameters to be characterized as diversely functionalized nanofibers because of their surface structure and their potential to modify their morphology and their

The electrospinning technique is very useful for the incorporation of drugs in drug delivery systems. This technique can be reproducible under controlled parameters and is used in many formulations for the creation of new and innovative drug carriers because of their efficiency of transporting the bioactive agents to the target without causing secondary effects in the body. There are different methods for incorporating therapeutic drugs into drug delivery systems with electrospinning, which can greatly influence the properties of the resulting drug-loaded fibrous system. These methods involve blending, coaxial, emulsion, and surface modification electrospinning, which have discrete advantages and disadvantages. According to the physicochemical properties of the drug, the polymeric characteristics and the application of the drug-incorporated fibers, such as the target zone and the required drug release rate, the appropriate method is being selected as not all drugs can be

Blending of the therapeutic agent with the appropriate polymeric solution remains the most predominant method for drug loading into nanofibers [3, 13]. This method is simple, compared to others, but some requirements should be met in order to gain the desired results. The polymeric blend improves the mechanical and physicochemical properties equilibrium of the drug-loaded nanofibers and increases effectively the formulation design for drug release, resulting in the manipulation of the release rate by changing the proportion of polymer in the blend [3, 15]. The insufficient solubility of the drug in the polymeric solution, where the drug molecules can shift to a nearby surface of fiber during electrospinning, can trigger the isolate release of the drug into the solution. Thus, the equilibrium among hydrophilic and hydrophobic properties between drugs and polymers is

#### *Electrospinning and Drug Delivery DOI: http://dx.doi.org/10.5772/intechopen.86181*

*Electrospinning and Electrospraying - Techniques and Applications*

tured nanofibers can be produced.

**2. Electrospinning**

polymer solution [1–6].

**2.1 Electrospinning equipment**

rotatable or static [2, 4, 5, 7–9].

*2.2.1 Electrospinning process*

**2.2 Electrospinning process and methods**

process [1–4], and upon the appropriate selection of the electrospinning apparatus and materials, diverse types of fibers, such as core-sheath, porous or hollow struc-

As already mentioned, electrospinning is a simple, highly versatile and robust technique for the production of polymers and a wide range of materials, including ceramic, metallic, and long fibers with diameters from submicron down to nanometer scale. These fibers are produced by feeding a polymer solution, dispersion or melt in a high electric field. It is worth mentioning that the use of melt in the electrospinning process is costly and leads to more difficult production than using

The main setup of an electrospinning equipment involves three main parts all enclosed within a chamber. A typical electrospinning apparatus is shown in **Figure 1**. It is composed of an electrical supply, for generating a high-voltage power supply, a piece of feeding equipment, which consists of a glass syringe with metallic needle filled with the polymer solution, a pump suitable for controlling the flow rate of the polymer solution, and a grounded collector usually made from aluminum foil. The power supply is used to apply tens of kilovolt to the needle, which works as a spinneret, while the pump extrudes the polymer from the syringe to the collector, which can be either

The working principle of electrospinning is straightforward: at ambient temperature, a polymer solution or melt is ejected from the tip of a needle to a grounded metal collector by applying high voltage between the needle and the collector [2]. In

*Typical schematic setup of electrospinning equipment with static (up) and rotatable collector (down).*

**32**

**Figure 1.**

detail, the electrospinning process starts with the application of high voltage, which creates electric charges that are moving toward the polymer solution in the syringe *via* the metallic needle. The induction of charges on the polymer droplet causes instability within the polymer solution, thus creating an electrically charged jet of polymer solution or melt. Concurrently, a force that opposes the surface tension is produced, by the mutual repulsion of charges, and as a result, the polymer solution flows in the direction of the electric field and is extruded from the needle of the syringe with the aid of a pump [4]. Specifically, the solution jet is ejected from the nozzle of the needle when the voltage exceeds a threshold value because the electric force overcomes the surface tension of the droplet. Each droplet is exposed to a high voltage, and a cone-shaped droplet is formed. This is known as the Taylor cone and is caused due to the electrical voltage, which is the difference voltage between the nozzle and the collector with the counter charge [8]. Subsequently, the charged jet of solution is evaporated or solidified before reaching the metallic collector, where the solid material is collected as a solid interconnected continuous network of small fibers [1, 8, 10]. Regarding the electrospinning process, a stable charge jet can be formed only if the polymer solution has adequate cohesive force. During the process, the internal and external charge forces cause the whipping of the liquid jet, thus permitting the polymer chains to stretch and slide into the solution pushing the jet toward the collector [4]. As a result, the created fibers have enough small diameters to be characterized as diversely functionalized nanofibers because of their surface structure and their potential to modify their morphology and their internal bulk content [1, 4, 11, 12].

#### *2.2.2 Electrospinning methods*

The electrospinning technique is very useful for the incorporation of drugs in drug delivery systems. This technique can be reproducible under controlled parameters and is used in many formulations for the creation of new and innovative drug carriers because of their efficiency of transporting the bioactive agents to the target without causing secondary effects in the body. There are different methods for incorporating therapeutic drugs into drug delivery systems with electrospinning, which can greatly influence the properties of the resulting drug-loaded fibrous system. These methods involve blending, coaxial, emulsion, and surface modification electrospinning, which have discrete advantages and disadvantages. According to the physicochemical properties of the drug, the polymeric characteristics and the application of the drug-incorporated fibers, such as the target zone and the required drug release rate, the appropriate method is being selected as not all drugs can be loaded with all of these methods [3, 13, 14].

#### *2.2.2.1 Blending electrospinning*

Blending of the therapeutic agent with the appropriate polymeric solution remains the most predominant method for drug loading into nanofibers [3, 13]. This method is simple, compared to others, but some requirements should be met in order to gain the desired results. The polymeric blend improves the mechanical and physicochemical properties equilibrium of the drug-loaded nanofibers and increases effectively the formulation design for drug release, resulting in the manipulation of the release rate by changing the proportion of polymer in the blend [3, 15]. The insufficient solubility of the drug in the polymeric solution, where the drug molecules can shift to a nearby surface of fiber during electrospinning, can trigger the isolate release of the drug into the solution. Thus, the equilibrium among hydrophilic and hydrophobic properties between drugs and polymers is

very important during blending electrospinning [3, 7]. The drug release behavior is highly contingent on the distribution of the drug molecule into electrospun nanofibers as well as on the morphology of the nanofibers. In order to achieve perfect encapsulation of the drug inside the electrospun nanofibers, the hydrophobic polyester polymers should interact very well with the hydrophobic or lipophilic drugs, such as rifampicin and paclitaxel, while the hydrophilic polymers, such as gelatin, polyethylene glycol (PEG), and polyvinyl alcohol (PVA), can dissolve hydrophilic drugs, such as doxorubicin. It has been cited that amphiphilic copolymers like the PEG-b-PLA diblock copolymer could significantly enhance drug-loading efficiency and subsequently reduce the burst release of drugs [13]. With the blending electrospinning method, the drug is dissolved or dispersed into the polymer solution to achieve drug encapsulation through a single-step electrospinning, and as a result, fibers are obtained with single phase only [3, 13].

#### *2.2.2.2 Coaxial electrospinning*

The coaxial electrospinning method is regarded as one of the most significant breakthroughs, and it is mainly useful for multidrug delivery systems, where the individual drug release behavior is controlled [2, 3, 13]. In this method, there are two liquids inside the spinneret, which minimize the interaction between aqueousbased biological molecules and the organic solvents, in which the polymer is mainly dissolved, and as a result is used for obtaining fibers with core-shell structures [2, 3, 13]. These structures are used in cases where the therapeutic agent is sensible to the environment [3]. Moreover, this method can be used for generating novel structural nanomaterials, such as preparing nanofibers from materials without filament-forming properties enclosing functional liquids within the fiber matrix and encapsulating drugs or biological agents in the core of the polymer nanofibers leading to sustained and controlled drug release [2, 3]. The functionality of biomolecules is improved in coaxial electrospinning because the inner jet is formed by the biomolecule solution, and the outer jet is formed by the polymer solution, which is the co-electrospun. Moreover, the polymeric shell contributes to the sustained and prolonged release of the therapeutic agent as well as protecting the ingredient in the core from direct exposure to the biological environment [3, 13]. In this method, the coaxial fibers have successfully loaded proteins, growth factor, antibiotics, and other biological agents for drug delivery purposes [3, 13]. In coaxial electrospinning, there are a lot of factors, which should be considered in the design step, such as shell and core polymer concentration, molecular weight, and drug concentration [13, 14]. Nevertheless, only a limited portion of the produced fibers can form the proper core/shell structure and this system improves the sustained release of drugs and allows the bioability of unstable biological agents to be maintained [3, 14].

#### *2.2.2.3 Emulsion electrospinning*

The emulsion electrospinning method is an important and flexible method for the encapsulation of several drugs into nanofibers as well as a cost-effective and efficient manner for preparing core-shell electrospun nanofibers [3, 14]. In the emulsion electrospinning method, the oil phase is created by the emulsion of the drug or aqueous protein solution in the hydrophobic polymer solution. At the end of the electrospinning, the biomolecule-loaded phase can be distributed within the fibers, if a low molecular weight drug is used, or a core-shell fibrous structure can be configured as macromolecules in the aqueous phase [3, 13, 14]. It has been reported that the ratio of hydrophilic (aqueous) to hydrophobic (polymer) solution is one of the parameters that affect the distribution of the biomolecules within

**35**

*Electrospinning and Drug Delivery*

*DOI: http://dx.doi.org/10.5772/intechopen.86181*

*2.2.2.4 Surface modification electrospinning*

**2.3 Electrospinning parameters**

the fibers. Moreover, it plays an important role in regulating the release profile, structural stability, and bioactivity of the encapsulated drug or proteins [3, 13, 14]. It is worth mentioning that the main advantage of emulsion electrospinning against blending electrospinning is the elimination of the need for a common solvent as the drug and the polymer are dissolved in applicable solvents. Numerous hydrophilic drugs and hydrophobic polymeric combinations can be used while maintaining minimal drug contact with the organic solvent during the procedure [3, 13, 14, 16]. However, the emulsion electrospinning would still cause damage or degradation of unstable macromolecules, like nucleic acids, mainly because of the shearing force and tension between the two phases of the emulsion, compared to coaxial electrospinning. Therefore, further modifications, like condensation of the carrier gene in gene therapy might be useful for more protection. Furthermore, during the emulsification or ultrasonication procedures in emulsion electrospinning, the contact of core materials with the solvent is increased, which may cause probable damage to the drug contents. Although extremely hydrophobic polymers can be used in emulsion electrospinning, the affinity or compatibility between drug and polymer might also influence the distribution of drugs within the fibers. It is cited that the copolymerization of hydrophobic polymers with hydrophilic polymers, such as PEG, ε-caprolactone (6-hexanolactone) (PCL), and poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) (PHBV), affects drug distribution [3, 13, 14].

The surface modification electrospinning is another promising method for introducing biofunctionality into nanofibers. In the surface modification electrospinning, a specific conductive surface can be chemically altered and changed aiming at modifying the external properties of a coated device, such as the tissue, which encircles the implanted material [3]. In this strategy, the release of the therapeutics is weakened and the functionality of the surface, where the immobilized biomolecules are located, preserved [13, 17]. Thus, this method is applied to avoid fast initial burst release and to slow down the rate of immobilization of the biological molecules on a particular surface. Therefore, the surface modification electrospinning is more applicable for gene or growth-factor delivery where slow and prolonged release of the therapeutic agent is required [13, 17]. Moreover, having a good electrospinning system and a well-standardized method, it is possible to coat 3D surfaces with nanoparticles or homogeneous surfaces [3, 16]. In cases where the drug cannot be immobilized, either because the drug is required to be endocytosed or interact with the nucleus of the cell, its release rate could be accurately controlled by introducing responsive materials to local external cues. This can happen by introducing hydrophobic functional groups onto the nanofibers surface [13].

The fabrication of nanofibers *via* electrospinning is affected by many different, but interlinked parameters as shown in **Table 1** [1]. These parameters modulate both the electrospinning process and the morphology of nanofibers [1, 4]. The electrospinning parameters can be classified as solution properties, process parameters, and environmental conditions [1, 4, 8]. The solution properties include the polymer concentration, molecular weight and viscosity, the solution conductivity and relative volatility, volatility of the solvent, surface tension, and dielectric constant. The process parameters refer to the flow rate, the applied voltage, the needle diameter, the distance between the tip of the needle and collector, and the geometry of the collector. The environmental conditions include the relative humidity and

#### *Electrospinning and Drug Delivery DOI: http://dx.doi.org/10.5772/intechopen.86181*

*Electrospinning and Electrospraying - Techniques and Applications*

fibers are obtained with single phase only [3, 13].

*2.2.2.2 Coaxial electrospinning*

*2.2.2.3 Emulsion electrospinning*

very important during blending electrospinning [3, 7]. The drug release behavior is highly contingent on the distribution of the drug molecule into electrospun nanofibers as well as on the morphology of the nanofibers. In order to achieve perfect encapsulation of the drug inside the electrospun nanofibers, the hydrophobic polyester polymers should interact very well with the hydrophobic or lipophilic drugs, such as rifampicin and paclitaxel, while the hydrophilic polymers, such as gelatin, polyethylene glycol (PEG), and polyvinyl alcohol (PVA), can dissolve hydrophilic drugs, such as doxorubicin. It has been cited that amphiphilic copolymers like the PEG-b-PLA diblock copolymer could significantly enhance drug-loading efficiency and subsequently reduce the burst release of drugs [13]. With the blending electrospinning method, the drug is dissolved or dispersed into the polymer solution to achieve drug encapsulation through a single-step electrospinning, and as a result,

The coaxial electrospinning method is regarded as one of the most significant breakthroughs, and it is mainly useful for multidrug delivery systems, where the individual drug release behavior is controlled [2, 3, 13]. In this method, there are two liquids inside the spinneret, which minimize the interaction between aqueousbased biological molecules and the organic solvents, in which the polymer is mainly dissolved, and as a result is used for obtaining fibers with core-shell structures [2, 3, 13].

The emulsion electrospinning method is an important and flexible method for the encapsulation of several drugs into nanofibers as well as a cost-effective and efficient manner for preparing core-shell electrospun nanofibers [3, 14]. In the emulsion electrospinning method, the oil phase is created by the emulsion of the drug or aqueous protein solution in the hydrophobic polymer solution. At the end of the electrospinning, the biomolecule-loaded phase can be distributed within the fibers, if a low molecular weight drug is used, or a core-shell fibrous structure can be configured as macromolecules in the aqueous phase [3, 13, 14]. It has been reported that the ratio of hydrophilic (aqueous) to hydrophobic (polymer) solution is one of the parameters that affect the distribution of the biomolecules within

These structures are used in cases where the therapeutic agent is sensible to the environment [3]. Moreover, this method can be used for generating novel structural nanomaterials, such as preparing nanofibers from materials without filament-forming properties enclosing functional liquids within the fiber matrix and encapsulating drugs or biological agents in the core of the polymer nanofibers leading to sustained and controlled drug release [2, 3]. The functionality of biomolecules is improved in coaxial electrospinning because the inner jet is formed by the biomolecule solution, and the outer jet is formed by the polymer solution, which is the co-electrospun. Moreover, the polymeric shell contributes to the sustained and prolonged release of the therapeutic agent as well as protecting the ingredient in the core from direct exposure to the biological environment [3, 13]. In this method, the coaxial fibers have successfully loaded proteins, growth factor, antibiotics, and other biological agents for drug delivery purposes [3, 13]. In coaxial electrospinning, there are a lot of factors, which should be considered in the design step, such as shell and core polymer concentration, molecular weight, and drug concentration [13, 14]. Nevertheless, only a limited portion of the produced fibers can form the proper core/shell structure and this system improves the sustained release of drugs and allows the bioability of unstable biological agents to be maintained [3, 14].

**34**

the fibers. Moreover, it plays an important role in regulating the release profile, structural stability, and bioactivity of the encapsulated drug or proteins [3, 13, 14]. It is worth mentioning that the main advantage of emulsion electrospinning against blending electrospinning is the elimination of the need for a common solvent as the drug and the polymer are dissolved in applicable solvents. Numerous hydrophilic drugs and hydrophobic polymeric combinations can be used while maintaining minimal drug contact with the organic solvent during the procedure [3, 13, 14, 16]. However, the emulsion electrospinning would still cause damage or degradation of unstable macromolecules, like nucleic acids, mainly because of the shearing force and tension between the two phases of the emulsion, compared to coaxial electrospinning. Therefore, further modifications, like condensation of the carrier gene in gene therapy might be useful for more protection. Furthermore, during the emulsification or ultrasonication procedures in emulsion electrospinning, the contact of core materials with the solvent is increased, which may cause probable damage to the drug contents. Although extremely hydrophobic polymers can be used in emulsion electrospinning, the affinity or compatibility between drug and polymer might also influence the distribution of drugs within the fibers. It is cited that the copolymerization of hydrophobic polymers with hydrophilic polymers, such as PEG, ε-caprolactone (6-hexanolactone) (PCL), and poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) (PHBV), affects drug distribution [3, 13, 14].

#### *2.2.2.4 Surface modification electrospinning*

The surface modification electrospinning is another promising method for introducing biofunctionality into nanofibers. In the surface modification electrospinning, a specific conductive surface can be chemically altered and changed aiming at modifying the external properties of a coated device, such as the tissue, which encircles the implanted material [3]. In this strategy, the release of the therapeutics is weakened and the functionality of the surface, where the immobilized biomolecules are located, preserved [13, 17]. Thus, this method is applied to avoid fast initial burst release and to slow down the rate of immobilization of the biological molecules on a particular surface. Therefore, the surface modification electrospinning is more applicable for gene or growth-factor delivery where slow and prolonged release of the therapeutic agent is required [13, 17]. Moreover, having a good electrospinning system and a well-standardized method, it is possible to coat 3D surfaces with nanoparticles or homogeneous surfaces [3, 16]. In cases where the drug cannot be immobilized, either because the drug is required to be endocytosed or interact with the nucleus of the cell, its release rate could be accurately controlled by introducing responsive materials to local external cues. This can happen by introducing hydrophobic functional groups onto the nanofibers surface [13].

#### **2.3 Electrospinning parameters**

The fabrication of nanofibers *via* electrospinning is affected by many different, but interlinked parameters as shown in **Table 1** [1]. These parameters modulate both the electrospinning process and the morphology of nanofibers [1, 4]. The electrospinning parameters can be classified as solution properties, process parameters, and environmental conditions [1, 4, 8]. The solution properties include the polymer concentration, molecular weight and viscosity, the solution conductivity and relative volatility, volatility of the solvent, surface tension, and dielectric constant. The process parameters refer to the flow rate, the applied voltage, the needle diameter, the distance between the tip of the needle and collector, and the geometry of the collector. The environmental conditions include the relative humidity and


#### **Table 1.**

*Parameters that affect the electrospinning technique.*

temperature [1, 4, 7, 8, 18]. The solution properties and the process parameters have predominant influence on the formation and morphology of the produced nanofibers, while the environmental conditions do not have a significant effect [1]. Moreover, all these factors are responsible for a flawless electrospinning process, which leads in the formation of the desirable electrospun nanofibers with the requisite characteristics [8]. Consequently, the careful monitoring of these factors can ensure the formation of smooth, highly porous nanofibers without beads [4, 8].

#### *2.3.1 Effects of polymer concentration*

The electrospinning method relies on the creation of electric charges in the polymer solution, which generate a charged jet [4]. When the polymer concentration is low, then the entangled polymer chains break into fragments before reaching the collector, due to the applied electric field and surface tension [4, 9, 12]. The entanglement of the polymer is necessary for fiber formation, but in the state of low polymer concentration. In this state, the phenomenon of electrospraying will take place and particles, instead of fibers, are formed [8, 19]. It has been reported that the boundary concentration between electrospray and electrospinning is solvent-dependent [8, 20]. Moreover, these polymer fragments cause the formation of nanofibers with beads [4]. In turn, if the polymer concentration increases, the

**37**

*2.3.4 Effects of surface tension*

*Electrospinning and Drug Delivery*

diameter [1, 4, 18, 22, 23].

*2.3.2 Effects of polymer viscosity*

*2.3.3 Effects of solution conductivity*

*DOI: http://dx.doi.org/10.5772/intechopen.86181*

chain entanglement among polymer chains will increase because of the increase in solution viscosity. As a result, these chain entanglements overcome the surface tension and uniform electrospun nanofibers devoid of beads are formed [4, 21]. If the concentration increases beyond a critical value, then the flow of the jet will be blocked as the droplet will dry out at the tip of the metallic needle, and the polymer jet would not be initiated. In this case, the clog should be removed to let the electrospinning process continue [4, 12, 18] and obtain beadles nanofibers with increased

With respect to the electrospinning method, the polymer viscosity is included in the solution properties. It has been reported that a change in polymer viscosity can affect the morphologies of the beads in nanofibers [4, 24]. If the viscosity of the polymer solution is low, the shape of the produced nanofibers will be round droplet like, but if the viscosity of the polymer solution is sufficient, then stretched droplet or eclipsed shapes fibers will be formed [4, 22–25]. Moreover, an increase in polymer concentration causes increase in polymer viscosity, and as a result, an increase beyond a critical value will block the flow of the jet and the droplet will dry out at the tip of the metallic needle. In conclusion, the determination of the critical value of viscosity is essential, as an increase in the polymer viscosity leads to thicker and bead-free nanofibers with increased diameter [4, 21]. Conversely, if the increase of

The solution conductivity is another solution parameter, which affects the electrospinning process and as a result the formation of nanofibers and their diameter distribution [7, 8]. The solution conductivity has a significant role on the formation of the Taylor cone and in controlling the diameter of the nanofibers [4, 8]. Poor conductivity solutions are not capable of producing electrospinning results, as the surface of the droplet will have no charge to form the Taylor cone. Conversely, an increase in the solution conductivity will lead to the Taylor cone formation because of the increase of the charge on the surface of the droplet. This will also lead to the reduction of the fiber diameter [4, 8, 26]. It has been reported that if the solution conductivity increases beyond a critical value, the formation of the Taylor cone will be prevented. This can be attributed to the Coulombic forces between the charges on the surface of the fluid and the force due to the external electric field [4]. It has been well documented that a highly conductive polymer solution is unstable and leads to a wide diameter distribution when a strong electric field is applied [4, 7, 27]. However, the polymer solution conductivity could be adjusted by the addition of a suitable salt [4, 7]. The addition of the salt affects the electrospinning process by increasing the number of the ions in the polymer solution resulting in the increase of surface charge density of the fluid and the electrostatic force produced by the applied electric field [4, 7, 22, 28, 29]. Moreover, the addition of the salt increases the polymer solution conductivity resulting in the reduction in the tangential electric field along the surface of the fluid [4]. Concluding, the increase of the solution conductivity leads to ultrafine nanofibers with reduced diameter [1, 7, 8, 26].

The surface tension is included in the solution parameters, which affect the electrospinning process and the nanofiber morphology, but there is no conclusive

viscosity is too high, beads will be generated in the nanofibers [1, 7].

#### *Electrospinning and Drug Delivery DOI: http://dx.doi.org/10.5772/intechopen.86181*

*Electrospinning and Electrospraying - Techniques and Applications*

temperature [1, 4, 7, 8, 18]. The solution properties and the process parameters have predominant influence on the formation and morphology of the produced nanofibers, while the environmental conditions do not have a significant effect [1]. Moreover, all these factors are responsible for a flawless electrospinning process, which leads in the formation of the desirable electrospun nanofibers with the requisite characteristics [8]. Consequently, the careful monitoring of these factors can ensure the formation of smooth, highly porous nanofibers without beads [4, 8].

The electrospinning method relies on the creation of electric charges in the polymer solution, which generate a charged jet [4]. When the polymer concentration is low, then the entangled polymer chains break into fragments before reaching the collector, due to the applied electric field and surface tension [4, 9, 12]. The entanglement of the polymer is necessary for fiber formation, but in the state of low polymer concentration. In this state, the phenomenon of electrospraying will take place and particles, instead of fibers, are formed [8, 19]. It has been reported that the boundary concentration between electrospray and electrospinning is solvent-dependent [8, 20]. Moreover, these polymer fragments cause the formation of nanofibers with beads [4]. In turn, if the polymer concentration increases, the

**36**

**Table 1.**

*2.3.1 Effects of polymer concentration*

*Parameters that affect the electrospinning technique.*

chain entanglement among polymer chains will increase because of the increase in solution viscosity. As a result, these chain entanglements overcome the surface tension and uniform electrospun nanofibers devoid of beads are formed [4, 21]. If the concentration increases beyond a critical value, then the flow of the jet will be blocked as the droplet will dry out at the tip of the metallic needle, and the polymer jet would not be initiated. In this case, the clog should be removed to let the electrospinning process continue [4, 12, 18] and obtain beadles nanofibers with increased diameter [1, 4, 18, 22, 23].

#### *2.3.2 Effects of polymer viscosity*

With respect to the electrospinning method, the polymer viscosity is included in the solution properties. It has been reported that a change in polymer viscosity can affect the morphologies of the beads in nanofibers [4, 24]. If the viscosity of the polymer solution is low, the shape of the produced nanofibers will be round droplet like, but if the viscosity of the polymer solution is sufficient, then stretched droplet or eclipsed shapes fibers will be formed [4, 22–25]. Moreover, an increase in polymer concentration causes increase in polymer viscosity, and as a result, an increase beyond a critical value will block the flow of the jet and the droplet will dry out at the tip of the metallic needle. In conclusion, the determination of the critical value of viscosity is essential, as an increase in the polymer viscosity leads to thicker and bead-free nanofibers with increased diameter [4, 21]. Conversely, if the increase of viscosity is too high, beads will be generated in the nanofibers [1, 7].

#### *2.3.3 Effects of solution conductivity*

The solution conductivity is another solution parameter, which affects the electrospinning process and as a result the formation of nanofibers and their diameter distribution [7, 8]. The solution conductivity has a significant role on the formation of the Taylor cone and in controlling the diameter of the nanofibers [4, 8]. Poor conductivity solutions are not capable of producing electrospinning results, as the surface of the droplet will have no charge to form the Taylor cone. Conversely, an increase in the solution conductivity will lead to the Taylor cone formation because of the increase of the charge on the surface of the droplet. This will also lead to the reduction of the fiber diameter [4, 8, 26]. It has been reported that if the solution conductivity increases beyond a critical value, the formation of the Taylor cone will be prevented. This can be attributed to the Coulombic forces between the charges on the surface of the fluid and the force due to the external electric field [4]. It has been well documented that a highly conductive polymer solution is unstable and leads to a wide diameter distribution when a strong electric field is applied [4, 7, 27]. However, the polymer solution conductivity could be adjusted by the addition of a suitable salt [4, 7]. The addition of the salt affects the electrospinning process by increasing the number of the ions in the polymer solution resulting in the increase of surface charge density of the fluid and the electrostatic force produced by the applied electric field [4, 7, 22, 28, 29]. Moreover, the addition of the salt increases the polymer solution conductivity resulting in the reduction in the tangential electric field along the surface of the fluid [4]. Concluding, the increase of the solution conductivity leads to ultrafine nanofibers with reduced diameter [1, 7, 8, 26].

#### *2.3.4 Effects of surface tension*

The surface tension is included in the solution parameters, which affect the electrospinning process and the nanofiber morphology, but there is no conclusive correlation [1]. Nevertheless, it has been reported that there is a delicate balance between the surface tension and the electric field (conductivity, concentration, and viscosity), which affects the ultimate morphology of the nanofibers [4, 7]. Particularly, the surface tension and the applied electric field cause the disentangling and breaking of the perplexed polymer chains into fragments before reaching the collector, which cause the formation of beads in the nanofibers [4, 9, 12]. Another case refers that the surface tension influences the surface of the polymeric nanofibers, and in the case of poor conductivity of polymers, charges accumulate onto the surface and as a result, beaded formation is prompted [7].

#### *2.3.5 Effects of molecular weight of polymer*

The molecular weight of the polymer is included in the solution properties, and it is a parameter that affects the viscosity of the solution. Ordinarily, an increase in molecular weight, until a critical value, leads to increase in solution viscosity and the formation of nanofibers with fewer beads [1, 7]. In general, polymers with high molecular weight are preferred as they cause extensive chain entanglement, which facilitates the nanofiber formation during the spinning process. On the contrary, polymer solutions with lower molecular weight may lead to the formation of beads or break up into droplets [30]. Overall, the molecular weight is one of the most important parameters, which affect the outcome nanofibers and as a result the electrospinning process.

#### *2.3.6 Effects of solvent volatility*

The solvent volatility is another parameter of solution parameters, which affects the electrospinning process and as a result the formation of smooth and beadles electrospun nanofibers. The solvents that are preferred in the electrospinning process should be polymers that are entirely soluble, and they should have moderate (appropriate) boiling point, which is related with the volatility of the solvent [4, 8]. Common volatile solvents, with high evaporation rates, which ensure the facile evaporation of the solvent from the tip of the needle to collector, are used in the electrospinning process [4]. The rate of solvent evaporation from the polymer solution jet leads to phase separation and creation of secondary structures on fibers [4, 7, 31]. It has been reported that highly volatile solvents absorb the heat from the jet, thus lowering the temperature of the liquid jet; this temperature drop decreases the thermodynamic stability of the nonsolvent phase. These phenomena result in high evaporation rates, which cause the drying of the jet at the tip of the needle, block the needle tip, and hence hinder the electrospinning process or else the early solidification of the polymer jet. Overall, highly volatile solvents are avoided in the electrospinning process because fiber formation will not be completed [4, 7, 8]. Similarly, solvents with low volatility should not be used, because they have high boiling points, which prevent the drying during the nanofiber jet formation or else the solidification process could be retarded because the solvent evaporation is low [4, 8]. Conclusively, the type of the solvent and especially their volatility profile, and the rate of evaporation are very important parameters for the formation of nanofibers. It is cited that higher volatility demands and higher flow rates result in the formation of electrospun nanofibers with fewer beads [1, 4, 7].

#### *2.3.7 Effects of solution volatility*

Relative volatility is a measure of the differences in volatility between two components and is used in the design of separation or absorption processes. The

**39**

*Electrospinning and Drug Delivery*

*2.3.8 Effects of dielectric constant*

nanofibers [1].

*2.3.9 Effects of flow rate*

of the fiber interrupts bead formation [1, 7].

*2.3.10 Effects of applied voltage*

*DOI: http://dx.doi.org/10.5772/intechopen.86181*

solution relative volatility is a solution parameter that has similar effect with the volatility of the solvent. Solutions that are prepared from solvents of very low volatility may deliver wet and cross-linked nanofibers or even no nanofibers, at all [4, 8, 30]. Conversely, the usage of highly volatile solvents for the solution preparation may result in intermittent spinning because of the solidification of the polymer jet at the tip of the needle [4, 7, 30]. It has been reported that an increase in relative volatility of polymer solution causes the appearance of porous microstructure due

The dielectric constant, sometimes called relative permittivity or specific inductive capacity, is the ratio of the permittivity of a substance to the permittivity of free space. It is an expression of the extent to which a material concentrates electric flux. The dielectric constant of the solvent(s), used in the successful electrospinning and the formation of electrospun nanofibers, has to be sufficient, but not high [1]. It has been reported that an increase in the dielectric constant of the solution leads to an increase of the number of jets. On the contrary, a reduction in the value of the dielectric constant to a single digit leads to the formation of a single jet. Furthermore, the value of the solution dielectric constant may influence the stability of the jet, as bending instability may be reduced with a lower charge density resulting in a longer and stable jet [30]. Overall, the solution dielectric constant has to be sufficient for the successful electrospinning and the formation of electrospun

The flow rate is an important parameter belonging to the process parameters, which influences the diameter of the electrospun fibers and subsequently the charge density and the morphology of the nanofibers [4, 7]. It is reported that there is a critical point depending on the polymeric solution, in which the critical flow rate leads to the formation of uniform electrospun nanofibers [4, 8]. In the case of increasing the flow rate, beyond the critical value, nanofibers with larger diameter and pore size are produced and the formation of beaded structures is enhanced [4, 7, 8, 18, 31]. This bead formation is caused due to the incomplete drying of the polymeric jet. When the delivery rate of the polymeric jet to the needle tip exceeds the rate at which the polymeric solution is removed from the tip by the electric force in the metallic collector, a mass balance shift results, which leads to a sustained but unstable jet and bead formation [4, 7, 32]. In the case of decreasing the flow rate, beyond the critical value, smooth, fine, and thinner nanofibers are formed [1, 18]. It is cited that increases and decreases in the flow rate affect the nanofiber formation, and as a result, a minimum flow rate of the polymeric solution is preferred in order to replace the solution that is lost with a new one, during jet formation, as the solution will have enough time for polarization, stretching, and drying [4, 31]. Overall, lowering the flow rate causes the formation of thinner nanofibers instead of too high flow rates in which the nanofiber diameter increases and the continuity

The applied voltage is an important process parameter, which affects the strength of the electric field and therefore influences the diameter and the nanofiber morphology [7, 8]. Moreover, an increase in the applied voltage causes a change

to higher volatility, and this affects fiber's porosity and morphology [7].

#### *Electrospinning and Drug Delivery DOI: http://dx.doi.org/10.5772/intechopen.86181*

*Electrospinning and Electrospraying - Techniques and Applications*

correlation [1]. Nevertheless, it has been reported that there is a delicate balance between the surface tension and the electric field (conductivity, concentration, and viscosity), which affects the ultimate morphology of the nanofibers [4, 7]. Particularly, the surface tension and the applied electric field cause the disentangling and breaking of the perplexed polymer chains into fragments before reaching the collector, which cause the formation of beads in the nanofibers [4, 9, 12]. Another case refers that the surface tension influences the surface of the polymeric nanofibers, and in the case of poor conductivity of polymers, charges accumulate

The molecular weight of the polymer is included in the solution properties, and it is a parameter that affects the viscosity of the solution. Ordinarily, an increase in molecular weight, until a critical value, leads to increase in solution viscosity and the formation of nanofibers with fewer beads [1, 7]. In general, polymers with high molecular weight are preferred as they cause extensive chain entanglement, which facilitates the nanofiber formation during the spinning process. On the contrary, polymer solutions with lower molecular weight may lead to the formation of beads or break up into droplets [30]. Overall, the molecular weight is one of the most important parameters, which affect the outcome nanofibers and as a result the

The solvent volatility is another parameter of solution parameters, which affects the electrospinning process and as a result the formation of smooth and beadles electrospun nanofibers. The solvents that are preferred in the electrospinning process should be polymers that are entirely soluble, and they should have moderate (appropriate) boiling point, which is related with the volatility of the solvent [4, 8]. Common volatile solvents, with high evaporation rates, which ensure the facile evaporation of the solvent from the tip of the needle to collector, are used in the electrospinning process [4]. The rate of solvent evaporation from the polymer solution jet leads to phase separation and creation of secondary structures on fibers [4, 7, 31]. It has been reported that highly volatile solvents absorb the heat from the jet, thus lowering the temperature of the liquid jet; this temperature drop decreases the thermodynamic stability of the nonsolvent phase. These phenomena result in high evaporation rates, which cause the drying of the jet at the tip of the needle, block the needle tip, and hence hinder the electrospinning process or else the early solidification of the polymer jet. Overall, highly volatile solvents are avoided in the electrospinning process because fiber formation will not be completed [4, 7, 8]. Similarly, solvents with low volatility should not be used, because they have high boiling points, which prevent the drying during the nanofiber jet formation or else the solidification process could be retarded because the solvent evaporation is low [4, 8]. Conclusively, the type of the solvent and especially their volatility profile, and the rate of evaporation are very important parameters for the formation of nanofibers. It is cited that higher volatility demands and higher flow rates result in

onto the surface and as a result, beaded formation is prompted [7].

the formation of electrospun nanofibers with fewer beads [1, 4, 7].

Relative volatility is a measure of the differences in volatility between two components and is used in the design of separation or absorption processes. The

*2.3.5 Effects of molecular weight of polymer*

electrospinning process.

*2.3.6 Effects of solvent volatility*

*2.3.7 Effects of solution volatility*

**38**

solution relative volatility is a solution parameter that has similar effect with the volatility of the solvent. Solutions that are prepared from solvents of very low volatility may deliver wet and cross-linked nanofibers or even no nanofibers, at all [4, 8, 30]. Conversely, the usage of highly volatile solvents for the solution preparation may result in intermittent spinning because of the solidification of the polymer jet at the tip of the needle [4, 7, 30]. It has been reported that an increase in relative volatility of polymer solution causes the appearance of porous microstructure due to higher volatility, and this affects fiber's porosity and morphology [7].

#### *2.3.8 Effects of dielectric constant*

The dielectric constant, sometimes called relative permittivity or specific inductive capacity, is the ratio of the permittivity of a substance to the permittivity of free space. It is an expression of the extent to which a material concentrates electric flux. The dielectric constant of the solvent(s), used in the successful electrospinning and the formation of electrospun nanofibers, has to be sufficient, but not high [1]. It has been reported that an increase in the dielectric constant of the solution leads to an increase of the number of jets. On the contrary, a reduction in the value of the dielectric constant to a single digit leads to the formation of a single jet. Furthermore, the value of the solution dielectric constant may influence the stability of the jet, as bending instability may be reduced with a lower charge density resulting in a longer and stable jet [30]. Overall, the solution dielectric constant has to be sufficient for the successful electrospinning and the formation of electrospun nanofibers [1].

#### *2.3.9 Effects of flow rate*

The flow rate is an important parameter belonging to the process parameters, which influences the diameter of the electrospun fibers and subsequently the charge density and the morphology of the nanofibers [4, 7]. It is reported that there is a critical point depending on the polymeric solution, in which the critical flow rate leads to the formation of uniform electrospun nanofibers [4, 8]. In the case of increasing the flow rate, beyond the critical value, nanofibers with larger diameter and pore size are produced and the formation of beaded structures is enhanced [4, 7, 8, 18, 31]. This bead formation is caused due to the incomplete drying of the polymeric jet. When the delivery rate of the polymeric jet to the needle tip exceeds the rate at which the polymeric solution is removed from the tip by the electric force in the metallic collector, a mass balance shift results, which leads to a sustained but unstable jet and bead formation [4, 7, 32]. In the case of decreasing the flow rate, beyond the critical value, smooth, fine, and thinner nanofibers are formed [1, 18]. It is cited that increases and decreases in the flow rate affect the nanofiber formation, and as a result, a minimum flow rate of the polymeric solution is preferred in order to replace the solution that is lost with a new one, during jet formation, as the solution will have enough time for polarization, stretching, and drying [4, 31]. Overall, lowering the flow rate causes the formation of thinner nanofibers instead of too high flow rates in which the nanofiber diameter increases and the continuity of the fiber interrupts bead formation [1, 7].

#### *2.3.10 Effects of applied voltage*

The applied voltage is an important process parameter, which affects the strength of the electric field and therefore influences the diameter and the nanofiber morphology [7, 8]. Moreover, an increase in the applied voltage causes a change in the shape of the Taylor cone, and as a result, a critical voltage, which depends on the polymeric solution, is needed for the formation of ultrafine nanofibers given a certain distance between the needle tip and collector [4, 5, 7, 8]. An increase in the applied voltage leads to the formation of thinner nanofibers because of the stretching of the polymer solution in correlation with the charge repulsion within the polymer jet [1, 4, 7, 18, 33]. A higher applied voltage, above the critical value, may lead to an irregular increase of the diameter and the formation of beaded, nonuniformity nanofibers [4, 7, 8, 22]. This situation is attributed to the decrease in the size of the Taylor cone and increase in the jet velocity, keeping the same flow rate [4, 22, 34]. However, there are studies that have shown that the increase in the applied voltage leads to increase in the diameter of the nanofibers [4, 18, 21]. This phenomenon may be explained as the increase of the voltage leads to the decrease of the volume of the drop at the tip of the needle causing the receding of the Taylor cone resulting in increase in the jet length and fiber diameter because of the increase in the amount of the ejected fluid and the flow rate of polymer solution [4, 18, 21]. In conclusion, in general, the increase of the applied voltage, until a critical value, causes the formation of thinner nanofibers, but this depends on the type of the polymeric solvent [1, 4, 7, 8, 18]. It is worth mentioning that the problem of bead formation was not solved by varying the applied voltage [18].

#### *2.3.11 Effects of needle tip to collector distance*

The distance between the metallic needle tip and the collector could be easily affecting the morphology of nanofibers because it is dependent on the deposition time, evaporation rate, and the whipping or instability interval [4, 7, 8, 35]. Therefore, a critical distance is needed to be fixed for the preparation of dry, smooth, and uniform electrospun nanofibers [1, 4]. A decrease in the distance between the tip and the collector leads to the enlargement of diameter of nanofibers and the generation of beads, while an increase in this distance leads to the formation of nanofibers with decreased diameter [1, 7, 8, 21, 35]. However, there are cases that the morphology of nanofibers is not affected by the distance between the metallic needle and the collector [4, 32]. Increasing the distance between the needle tip and the collector, the nanofiber diameter decreases and there is a minimum distance required to obtain dry, smooth, and uniform electrospun nanofibers, but when the distance is too short or too large, beads are formed [1, 7].

#### *2.3.12 Effects of relative humidity*

The relative humidity is a factor belonging to the environmental conditions of the electrospinning, which affects the diameter and the morphology of the electrospun nanofibers [4, 8, 36, 37]. The relative humidity is crucial for the production of ultrafine nanofibers with acceptable morphology, because it affects the formation of pores on the fiber surface *via* solvent evaporation or else controlling the solidification process of the charged jet [4, 7, 8]. The appropriate amount of the relative humidity depends on the chemical nature of the used polymer. A high relative humidity suppresses the evaporation rate as long as the surface area of the jet increases and the charge per unit area on the surface of the jet decreases resulting in the capillary instability and the beaded structure formation [1, 7, 8]. It has been cited that humidity controls the evaporation rate of the fluid jet when the water is used as a solvent component [7]. Overall, lower relative humidity enables higher flow rate, and as a result, the formation of beads is reduced, while higher relative humidity leads to the appearance of porous microstructures due to evaporation effects and/or phase separation [1, 7, 8].

**41**

*Electrospinning and Drug Delivery*

*2.3.13 Effects of temperature*

are summarized in **Table 2**.

tion [1, 4, 8].

*DOI: http://dx.doi.org/10.5772/intechopen.86181*

**3. Electrospinning in** *per* **oral drug delivery**

release systems and more recently in modified release systems.

**3.1 Electrospinning in controlled** *per* **oral drug delivery**

The temperature is another factor belonging to the environmental conditions of the electrospinning, which is crucial for the production of ultrafine nanofibers with acceptable morphology, because it affects the diameter of the fibers [4, 8, 36, 37]. Moreover, temperature causes changes in the average diameter of the nanofibers resulting in modification of the electrospun nanofibers size by causing two opposing effects; first, it increases the evaporation rate of the solvent and secondly, it decreases the viscosity of the polymer solution. These effects have the behavior of two opposite mechanisms, but both of them lead to a mean fiber diameter decrease [4, 8]. In general, an increase in the temperature leads to thinner nanofibers forma-

With the appearance of nanotechnology, researchers have become more attracted in studying the characteristic properties of nanoscale materials.

Electrospinning, a method of electrostatic fiber fabrication, has established more attention in recent years due to its usefulness and potential for applications in diverse fields, like tissue engineering, biosensors, filtration, wound dressings, drug delivery, and enzyme immobilization. The nanoscale fibers are generated by the application of strong electric fields on polymer solution and mimic better the extracellular matrix components as compared to the conventional techniques, offering various advantages, like high surface area to volume ratio, tunable porosity, and the ability to manipulate nanofiber composition in order to get desired properties and function [38]. The use of electrospun nanofibers, as formulation systems for oral drug delivery, has been studied extensively over the past decades in fast/immediate

Numerous researchers have been studying orodispersible or fast-dissolving drug delivery formulations produced from nanofiber-loaded systems that rapidly disintegrate in the oral cavity due to nanofibers' large surface area, which causes immediate disintegration in water solutions and fast drug release [18, 39–46]. Applications of the electrospinning technique on modified *per* oral drug delivery

Oral controlled drug release systems are characteristic in formulation, and researchers have developed electrospun nanofibers for usage in treatment and management of disorders that need special drug release patterns. Scientists have developed amyloid-like bovine serum albumin with ampicillin sodium salt nanofibers by electrospinning, and the *in vitro* results showed controlled release behavior [47]. Electrospun fiber mats were also investigated as drug delivery systems using tetracycline hydrochloride as a model drug. The nanofibers were made either from poly(lactic acid), poly(ethylene-co-vinyl acetate), or from a 50:50 blend of the two. The release of the tetracycline hydrochloride from these new drug delivery systems followed controlled release behavior [48]. Moreover, polyvinyl alcohol nanofibers loaded with curcumin or its *β*-cyclodextrin inclusion complexes were prepared using an electrospinning process. *In vitro* dissolution tests showed that the drug release profiles of polyvinyl alcohol/curcumin and polyvinyl alcohol/complex fibers were different, with release from the latter occurring more rapidly [49]. In addition, electrospun gelatin nanofibers were prepared by sequential crosslinking

#### *2.3.13 Effects of temperature*

*Electrospinning and Electrospraying - Techniques and Applications*

in the shape of the Taylor cone, and as a result, a critical voltage, which depends on the polymeric solution, is needed for the formation of ultrafine nanofibers given a certain distance between the needle tip and collector [4, 5, 7, 8]. An increase in the applied voltage leads to the formation of thinner nanofibers because of the stretching of the polymer solution in correlation with the charge repulsion within the polymer jet [1, 4, 7, 18, 33]. A higher applied voltage, above the critical value, may lead to an irregular increase of the diameter and the formation of beaded, nonuniformity nanofibers [4, 7, 8, 22]. This situation is attributed to the decrease in the size

of the Taylor cone and increase in the jet velocity, keeping the same flow rate [4, 22, 34]. However, there are studies that have shown that the increase in the applied voltage leads to increase in the diameter of the nanofibers [4, 18, 21]. This phenomenon may be explained as the increase of the voltage leads to the decrease of the volume of the drop at the tip of the needle causing the receding of the Taylor cone resulting in increase in the jet length and fiber diameter because of the increase in the amount of the ejected fluid and the flow rate of polymer solution [4, 18, 21]. In conclusion, in general, the increase of the applied voltage, until a critical value, causes the formation of thinner nanofibers, but this depends on the type of the polymeric solvent [1, 4, 7, 8, 18]. It is worth mentioning that the problem

of bead formation was not solved by varying the applied voltage [18].

The distance between the metallic needle tip and the collector could be easily affecting the morphology of nanofibers because it is dependent on the deposition time, evaporation rate, and the whipping or instability interval [4, 7, 8, 35]. Therefore, a critical distance is needed to be fixed for the preparation of dry, smooth, and uniform electrospun nanofibers [1, 4]. A decrease in the distance between the tip and the collector leads to the enlargement of diameter of nanofibers and the generation of beads, while an increase in this distance leads to the formation of nanofibers with decreased diameter [1, 7, 8, 21, 35]. However, there are cases that the morphology of nanofibers is not affected by the distance between the metallic needle and the collector [4, 32]. Increasing the distance between the needle tip and the collector, the nanofiber diameter decreases and there is a minimum distance required to obtain dry, smooth, and uniform electrospun nanofibers, but when the

The relative humidity is a factor belonging to the environmental conditions of the electrospinning, which affects the diameter and the morphology of the electrospun nanofibers [4, 8, 36, 37]. The relative humidity is crucial for the production of ultrafine nanofibers with acceptable morphology, because it affects the formation of pores on the fiber surface *via* solvent evaporation or else controlling the solidification process of the charged jet [4, 7, 8]. The appropriate amount of the relative humidity depends on the chemical nature of the used polymer. A high relative humidity suppresses the evaporation rate as long as the surface area of the jet increases and the charge per unit area on the surface of the jet decreases resulting in the capillary instability and the beaded structure formation [1, 7, 8]. It has been cited that humidity controls the evaporation rate of the fluid jet when the water is used as a solvent component [7]. Overall, lower relative humidity enables higher flow rate, and as a result, the formation of beads is reduced, while higher relative humidity leads to the appearance of porous microstructures due to evaporation

*2.3.11 Effects of needle tip to collector distance*

distance is too short or too large, beads are formed [1, 7].

*2.3.12 Effects of relative humidity*

effects and/or phase separation [1, 7, 8].

**40**

The temperature is another factor belonging to the environmental conditions of the electrospinning, which is crucial for the production of ultrafine nanofibers with acceptable morphology, because it affects the diameter of the fibers [4, 8, 36, 37]. Moreover, temperature causes changes in the average diameter of the nanofibers resulting in modification of the electrospun nanofibers size by causing two opposing effects; first, it increases the evaporation rate of the solvent and secondly, it decreases the viscosity of the polymer solution. These effects have the behavior of two opposite mechanisms, but both of them lead to a mean fiber diameter decrease [4, 8]. In general, an increase in the temperature leads to thinner nanofibers formation [1, 4, 8].

#### **3. Electrospinning in** *per* **oral drug delivery**

With the appearance of nanotechnology, researchers have become more attracted in studying the characteristic properties of nanoscale materials. Electrospinning, a method of electrostatic fiber fabrication, has established more attention in recent years due to its usefulness and potential for applications in diverse fields, like tissue engineering, biosensors, filtration, wound dressings, drug delivery, and enzyme immobilization. The nanoscale fibers are generated by the application of strong electric fields on polymer solution and mimic better the extracellular matrix components as compared to the conventional techniques, offering various advantages, like high surface area to volume ratio, tunable porosity, and the ability to manipulate nanofiber composition in order to get desired properties and function [38]. The use of electrospun nanofibers, as formulation systems for oral drug delivery, has been studied extensively over the past decades in fast/immediate release systems and more recently in modified release systems.

Numerous researchers have been studying orodispersible or fast-dissolving drug delivery formulations produced from nanofiber-loaded systems that rapidly disintegrate in the oral cavity due to nanofibers' large surface area, which causes immediate disintegration in water solutions and fast drug release [18, 39–46]. Applications of the electrospinning technique on modified *per* oral drug delivery are summarized in **Table 2**.

#### **3.1 Electrospinning in controlled** *per* **oral drug delivery**

Oral controlled drug release systems are characteristic in formulation, and researchers have developed electrospun nanofibers for usage in treatment and management of disorders that need special drug release patterns. Scientists have developed amyloid-like bovine serum albumin with ampicillin sodium salt nanofibers by electrospinning, and the *in vitro* results showed controlled release behavior [47]. Electrospun fiber mats were also investigated as drug delivery systems using tetracycline hydrochloride as a model drug. The nanofibers were made either from poly(lactic acid), poly(ethylene-co-vinyl acetate), or from a 50:50 blend of the two. The release of the tetracycline hydrochloride from these new drug delivery systems followed controlled release behavior [48]. Moreover, polyvinyl alcohol nanofibers loaded with curcumin or its *β*-cyclodextrin inclusion complexes were prepared using an electrospinning process. *In vitro* dissolution tests showed that the drug release profiles of polyvinyl alcohol/curcumin and polyvinyl alcohol/complex fibers were different, with release from the latter occurring more rapidly [49]. In addition, electrospun gelatin nanofibers were prepared by sequential crosslinking


#### **Table 2.**

*An overview of the electrospinning technique applications in modified per oral drug delivery.*

using piperine as a hydrophobic model drug by sandwiching the drug-loaded gelatin nanofiber mesh with another gelatin nanofiber matrix without drug (acting as diffusion barrier). The results indicated controlled and sustainable release of the drug for prolonged time [50]. Researchers have also prepared melatoninloaded nanofibrous systems based on cellulose acetate, polyvinylpyrrolidone, and hydroxypropylmethylcellulose. The electrospun nanofiber mats that were inserted

**43**

*Electrospinning and Drug Delivery*

*DOI: http://dx.doi.org/10.5772/intechopen.86181*

in hard gelatin capsules exhibited variable release profiles in the gastric-like fluids, ranging from 30 to 120 min, while the electrospun nanofiber mats that were inserted in DRcaps™ capsules released melatonin at a slower pace [51]. In another study, nanofibers of cellulose acetate and polyvinylpyrrolidone loaded with melatonin were prepared and compressed at various pressures into monolayered tablets. The nanofiber mats were then incorporated into three-layered tablets, containing in the upper and lower layer combinations of lactose monohydrate and hydroxypropylmethylcellulose, as modifying accessories, and their *in vitro* dissolution profiles

Besides controlled drug release, researchers have investigated electrospun nanofibers as oral delivery systems for delayed release systems. In a study, both fast dissolving and sustained release drug delivery systems comprising mebeverine hydrochloride embedded in either povidone K60 or Eudragit RL 100–55 nanofibers have been prepared by electrospinning. The *in vitro* dissolution tests of the povidone K60 fiber mats revealed dissolution within 10 s, while the Eudragit fibers revealed pH-dependent drug release profiles, with only very limited release at pH 2.0, but sustained release over approximately 8 h at pH 6.8. As a result, it can be stated that the Eudragit nanofibers have the potential to be developed as oral drug delivery systems for localized drug release in the intestinal tract, whereas the povidone materials may find application as buccal delivery systems or suppositories [53]. Various researchers have synthesized gelatin nanofibers by electrospinning, using piperine as a hydrophobic model drug. The electrospun gelatin nanofibers were cross-linked by exposing to saturated glutaraldehyde vapor, to improve their water-resistive properties. The results illustrated good compatibility of the hydrophobic drug in gelatin nanofibers with promising controlled drug release patterns by varying crosslinking time and the pH of the release medium [54]. In another scientific report, a solvent-based electrospinning method was used to prepare nanofiber-based capsules including drugs (uranine was used as a water-soluble drug and nifedipine as a water-insoluble drug) for controlled release delivery systems using methacrylic acid copolymer as a polymer. The *in vitro* release of uranine or nifedipine from the nanofiber-packed capsules and milled powder of nanofiber-packed capsules showed controlled release of uranine or nifedipine, as compared to capsules of a physical mixture of methacrylic acid copolymer and each drug. The *in vivo* pharmacokinetic evaluation in rats, after intraduodenal administration of nanofiber-packed capsules or milled powder of nanofiber-packed capsules including uranine and/or nifedipine, clearly demonstrated that the application of the nanofibrotic technique, as a drug delivery system, offers drastic changes in pharmacokinetic profiles for both water-soluble and water-insoluble drugs [55]. Furthermore, nanofibers made from methacrylic acid copolymer S, containing acetaminophen, were prepared using a solvent-based electrospinning method. The *in vitro* dissolution rate profiles of acetaminophen showed that the tablets based on methacrylic acid copolymer S nanofibers did not disintegrate in the intestine in the lower pH region and could

have showed promising results in modified *per* oral drug delivery [52].

**3.2 Electrospinning in delayed** *per* **oral drug delivery**

regulate the drug release in a pH-dependent manner [56].

**3.3 Electrospinning in colon-targeted** *per* **oral drug delivery**

In addition to the previously described drug delivery systems, many scientists have demonstrated that the electrospinning method could be regarded as a modern approach for the preparation of colon drug delivery systems leading to marketable products. Eudragit L 100-55 nanofibers loaded with diclofenac sodium were

#### *Electrospinning and Drug Delivery DOI: http://dx.doi.org/10.5772/intechopen.86181*

*Electrospinning and Electrospraying - Techniques and Applications*

using piperine as a hydrophobic model drug by sandwiching the drug-loaded gelatin nanofiber mesh with another gelatin nanofiber matrix without drug (acting as diffusion barrier). The results indicated controlled and sustainable release of the drug for prolonged time [50]. Researchers have also prepared melatoninloaded nanofibrous systems based on cellulose acetate, polyvinylpyrrolidone, and hydroxypropylmethylcellulose. The electrospun nanofiber mats that were inserted

*An overview of the electrospinning technique applications in modified per oral drug delivery.*

**42**

**Table 2.**

in hard gelatin capsules exhibited variable release profiles in the gastric-like fluids, ranging from 30 to 120 min, while the electrospun nanofiber mats that were inserted in DRcaps™ capsules released melatonin at a slower pace [51]. In another study, nanofibers of cellulose acetate and polyvinylpyrrolidone loaded with melatonin were prepared and compressed at various pressures into monolayered tablets. The nanofiber mats were then incorporated into three-layered tablets, containing in the upper and lower layer combinations of lactose monohydrate and hydroxypropylmethylcellulose, as modifying accessories, and their *in vitro* dissolution profiles have showed promising results in modified *per* oral drug delivery [52].

#### **3.2 Electrospinning in delayed** *per* **oral drug delivery**

Besides controlled drug release, researchers have investigated electrospun nanofibers as oral delivery systems for delayed release systems. In a study, both fast dissolving and sustained release drug delivery systems comprising mebeverine hydrochloride embedded in either povidone K60 or Eudragit RL 100–55 nanofibers have been prepared by electrospinning. The *in vitro* dissolution tests of the povidone K60 fiber mats revealed dissolution within 10 s, while the Eudragit fibers revealed pH-dependent drug release profiles, with only very limited release at pH 2.0, but sustained release over approximately 8 h at pH 6.8. As a result, it can be stated that the Eudragit nanofibers have the potential to be developed as oral drug delivery systems for localized drug release in the intestinal tract, whereas the povidone materials may find application as buccal delivery systems or suppositories [53]. Various researchers have synthesized gelatin nanofibers by electrospinning, using piperine as a hydrophobic model drug. The electrospun gelatin nanofibers were cross-linked by exposing to saturated glutaraldehyde vapor, to improve their water-resistive properties. The results illustrated good compatibility of the hydrophobic drug in gelatin nanofibers with promising controlled drug release patterns by varying crosslinking time and the pH of the release medium [54]. In another scientific report, a solvent-based electrospinning method was used to prepare nanofiber-based capsules including drugs (uranine was used as a water-soluble drug and nifedipine as a water-insoluble drug) for controlled release delivery systems using methacrylic acid copolymer as a polymer. The *in vitro* release of uranine or nifedipine from the nanofiber-packed capsules and milled powder of nanofiber-packed capsules showed controlled release of uranine or nifedipine, as compared to capsules of a physical mixture of methacrylic acid copolymer and each drug. The *in vivo* pharmacokinetic evaluation in rats, after intraduodenal administration of nanofiber-packed capsules or milled powder of nanofiber-packed capsules including uranine and/or nifedipine, clearly demonstrated that the application of the nanofibrotic technique, as a drug delivery system, offers drastic changes in pharmacokinetic profiles for both water-soluble and water-insoluble drugs [55]. Furthermore, nanofibers made from methacrylic acid copolymer S, containing acetaminophen, were prepared using a solvent-based electrospinning method. The *in vitro* dissolution rate profiles of acetaminophen showed that the tablets based on methacrylic acid copolymer S nanofibers did not disintegrate in the intestine in the lower pH region and could regulate the drug release in a pH-dependent manner [56].

#### **3.3 Electrospinning in colon-targeted** *per* **oral drug delivery**

In addition to the previously described drug delivery systems, many scientists have demonstrated that the electrospinning method could be regarded as a modern approach for the preparation of colon drug delivery systems leading to marketable products. Eudragit L 100-55 nanofibers loaded with diclofenac sodium were

successfully prepared using an electrospinning process. *In vitro* dissolution tests verified that all the drug-loaded Eudragit L 100-55 nanofibers had pH-dependent drug release profiles, with limited release at pH 1.0, but a sustained and complete release at pH 6.8, indicating the potential of oral colon-targeted drug delivery systems development [57]. Researchers prepared medicated shellac nanofibers providing colon-specific sustained release of ferulic acid using coaxial electrospinning. The *in vitro* dissolution tests demonstrated that there was minimal ferulic acid release at pH 2.0, and sustained release in a neutral dissolution medium [58]. Another group of researchers have prepared electrospun nanofibers of indomethacin aimed for colon delivery using Eudragit S and Eudragit RS as polymers. It was shown that the ratio of drug:polymer and polymer:polymer were pivotal factors to control the drug release from nanofibers. A formulation containing Eudragit S:Eudragit RS (60:40) and drug:polymer ratio of 3:5 exhibited the most appropriate drug release, as a colon delivery system with a minor release at pH 1.2, 6.4, and 6.8 and a major release at pH 7.4 [59]. Electrospun nanofibers were also successfully prepared using indomethacin as a drug and Eudragit RS100 and S100 as polymers for colonic drug delivery [60]. Moreover, celecoxib-loaded electrospun nanofibers were developed using a combination of time-dependent polymers with pectin to achieve colon-specific drug delivery systems. The drug release was limited in the acidic media; while, in the simulated colonic media, it was higher from formulations containing the excipient pectin [61]. Likewise, electrospun fibers loaded with budesonide were prepared with the aim of controlling its release in the gastrointestinal tract using Eudragit RS 100, a polymer soluble at pH > 7, commonly used for enteric release of drugs. The dissolution rate measurements using a pH-change method showed low drug dissolution at pH 1.0 and sustained release at pH 7.2, representing an effective method for drug targeting to terminal ileum and colon with the aim of improving the local efficacy of budesonide for the treatment of some inflammatory bowel diseases [62]. Researchers have developed a novel core-shell-structured nanofilm for colon delivery by coaxial electrospinning using bovine serum albumin as protein model. First, the proteinloaded chitosan nanoparticle was prepared by ionic gelation, and then, the coaxial nanofilm was fabricated using alginate as shell layer and the protein-loaded chitosan nanoparticle as core layer. The protein release in different simulated digestive fluids revealed that the electrospun nanofilm is a promising colon-specific delivery system for bioactive proteins [63]. Another group of scientists reported in their work that the pH-responsive drug delivery systems could mediate drug releasing rate by changing the pH values at specific times as *per* the pathophysiological need of the disease. Their study demonstrated that a mussel-inspired protein polydopamine coating can tune the loading and releasing rate of charged molecules from electrospun poly(ε-caprolactone) nanofibers in solutions with different pH values. The *in vitro* release profiles showed that the positively charged molecules led to a significantly faster release in acidic than in neutral and basic media, while the results of specialized assays showed that the media containing doxorubicin released in solutions at low pH values could kill a significantly higher number of cells than those released in solutions at higher pH values. The pH-responsive drug delivery systems based on polydopamine-coated poly(e-caprolactone) nanofibers could have potential application in the oral delivery of anticancer drugs for treating gastric cancer and in vaginal delivery of antiviral or anti-inflammatory drugs, which could raise their efficacy, deliver them to the specific site, and minimize their toxicity [64].

#### **3.4 Electrospinning in biphasic and dual** *per* **oral drug delivery**

More to the point of modified drug delivery systems, researchers have designed and fabricated nanostructures using electrospinning for providing biphasic drug

**45**

**4. Conclusions**

*Electrospinning and Drug Delivery*

*DOI: http://dx.doi.org/10.5772/intechopen.86181*

release profiles. A research work investigated the biphasic release profile of ketoprofen of core/sheath nanofibers prepared using as polymers polyvinylpyrrolidone for the sheath and ethyl cellulose for the core matrix by coaxial electrospinning. The *in vitro* dissolution tests showed that the nanofibers produced could provide a biphasic drug release profile consisting of an immediate and a sustained release [65]. In another work, core-sheath nanofibers were also prepared using ketoprofen as a model drug, and polyvinylpyrrolidone and zein as the sheath polymer and core matrix excipient, respectively, by coaxial electrospinning. The *in vitro* dissolution tests showed that the nanofibers could provide an immediate release of 42.3% of the drug followed by a sustained release over 10 h of the remaining drug [66]. Other researchers have used simple sequential electrospinning to create a triple layered nanofiber mesh with biphasic drug release behavior. The mesh was composed of zein and polyvinylpyrrolidone as the top/bottom and middle layers, respectively. Ketoprofen was used as a model drug, and polyvinylpyrrolidone was blended with graphene oxide to improve the drug release functionality of the nanofiber as well as its mechanical properties. The *in vitro* release tests demonstrated time-regulated biphasic drug release [67]. In another study, gelatin-ciprofloxacin nanofibers containing various amounts of ciprofloxacin were fabricated on the surface of Mg-Ca alloy *via* an electrospinning process. Prolonged drug release was attained from gelatin-ciprofloxacin nanofibers coating along with initial rapid drug release of around 20–22% during 12 h, followed by a slow release stage that can effectively control the infection [68]. Moreover, resveratrol (a promising natural substance for periodontal disease treatment due to its anti-inflammatory and antioxidative effects) was successfully incorporated into polycaprolactone-nanofibers and enabled a biphasic-release kinetic pattern [69]. In a recent study, it was demonstrated that the production of core-shell fibers via modified coaxial electrospinning achieved controlled release of ampicillin-loaded polycaprolactone nanofibers covered by a polycaprolactone shield. The *in vitro* release studies showed that the drug release kinetics of core-shell products is closer to zero-order kinetics, while the drug release kinetics of single electrospinning of the core resulted with burst release [70]. Scientists have also used piroxicam as a low-dose, poorly soluble drug and hydroxypropyl methylcellulose as an amorphous-state stabilizing carrier polymer in

nanofibers to produce biphasic-release drug delivery systems [71].

nonsteroidal anti-inflammatory drugs [72].

Dual drug delivery systems have also been successfully developed by researchers. In a recent study, aceclofenac/pantoprazole-loaded zein/Eudragit S 100 nanofibers were developed using a single nozzle electrospinning process. The *in vitro* release studies ensured the efficiency of the nanofibers in sustaining the release of both drugs up to 8 h, while the *in vivo* experiments confirmed that the co-administration of pantoprazole and aceclofenac reduced the gastrointestinal toxicity induced by

The fabrication of electrospun ultrafine fiber meshes from biodegradable and biocompatible polymers has opened new horizons in the biomedical field. Electrospinning, being a simple, highly versatile, and robust technique for the production of fibers with diameters from submicron down to nanometer scale, could provide a useful method for the development of novel drug carriers capable of affecting the drugs' modified release. By careful selection of polymers, it is now possible to deliver drugs, with diverse stereoelectronic and physicochemical properties, in a required manner using electrospun nanofibers. *Mutatis mutandis*, in order to make further progress in the drug delivery field, it is necessary to identify ways that

#### *Electrospinning and Drug Delivery DOI: http://dx.doi.org/10.5772/intechopen.86181*

*Electrospinning and Electrospraying - Techniques and Applications*

deliver them to the specific site, and minimize their toxicity [64].

**3.4 Electrospinning in biphasic and dual** *per* **oral drug delivery**

More to the point of modified drug delivery systems, researchers have designed and fabricated nanostructures using electrospinning for providing biphasic drug

successfully prepared using an electrospinning process. *In vitro* dissolution tests verified that all the drug-loaded Eudragit L 100-55 nanofibers had pH-dependent drug release profiles, with limited release at pH 1.0, but a sustained and complete release at pH 6.8, indicating the potential of oral colon-targeted drug delivery systems development [57]. Researchers prepared medicated shellac nanofibers providing colon-specific sustained release of ferulic acid using coaxial electrospinning. The *in vitro* dissolution tests demonstrated that there was minimal ferulic acid release at pH 2.0, and sustained release in a neutral dissolution medium [58]. Another group of researchers have prepared electrospun nanofibers of indomethacin aimed for colon delivery using Eudragit S and Eudragit RS as polymers. It was shown that the ratio of drug:polymer and polymer:polymer were pivotal factors to control the drug release from nanofibers. A formulation containing Eudragit S:Eudragit RS (60:40) and drug:polymer ratio of 3:5 exhibited the most appropriate drug release, as a colon delivery system with a minor release at pH 1.2, 6.4, and 6.8 and a major release at pH 7.4 [59]. Electrospun nanofibers were also successfully prepared using indomethacin as a drug and Eudragit RS100 and S100 as polymers for colonic drug delivery [60]. Moreover, celecoxib-loaded electrospun nanofibers were developed using a combination of time-dependent polymers with pectin to achieve colon-specific drug delivery systems. The drug release was limited in the acidic media; while, in the simulated colonic media, it was higher from formulations containing the excipient pectin [61]. Likewise, electrospun fibers loaded with budesonide were prepared with the aim of controlling its release in the gastrointestinal tract using Eudragit RS 100, a polymer soluble at pH > 7, commonly used for enteric release of drugs. The dissolution rate measurements using a pH-change method showed low drug dissolution at pH 1.0 and sustained release at pH 7.2, representing an effective method for drug targeting to terminal ileum and colon with the aim of improving the local efficacy of budesonide for the treatment of some inflammatory bowel diseases [62]. Researchers have developed a novel core-shell-structured nanofilm for colon delivery by coaxial electrospinning using bovine serum albumin as protein model. First, the proteinloaded chitosan nanoparticle was prepared by ionic gelation, and then, the coaxial nanofilm was fabricated using alginate as shell layer and the protein-loaded chitosan nanoparticle as core layer. The protein release in different simulated digestive fluids revealed that the electrospun nanofilm is a promising colon-specific delivery system for bioactive proteins [63]. Another group of scientists reported in their work that the pH-responsive drug delivery systems could mediate drug releasing rate by changing the pH values at specific times as *per* the pathophysiological need of the disease. Their study demonstrated that a mussel-inspired protein polydopamine coating can tune the loading and releasing rate of charged molecules from electrospun poly(ε-caprolactone) nanofibers in solutions with different pH values. The *in vitro* release profiles showed that the positively charged molecules led to a significantly faster release in acidic than in neutral and basic media, while the results of specialized assays showed that the media containing doxorubicin released in solutions at low pH values could kill a significantly higher number of cells than those released in solutions at higher pH values. The pH-responsive drug delivery systems based on polydopamine-coated poly(e-caprolactone) nanofibers could have potential application in the oral delivery of anticancer drugs for treating gastric cancer and in vaginal delivery of antiviral or anti-inflammatory drugs, which could raise their efficacy,

**44**

release profiles. A research work investigated the biphasic release profile of ketoprofen of core/sheath nanofibers prepared using as polymers polyvinylpyrrolidone for the sheath and ethyl cellulose for the core matrix by coaxial electrospinning. The *in vitro* dissolution tests showed that the nanofibers produced could provide a biphasic drug release profile consisting of an immediate and a sustained release [65]. In another work, core-sheath nanofibers were also prepared using ketoprofen as a model drug, and polyvinylpyrrolidone and zein as the sheath polymer and core matrix excipient, respectively, by coaxial electrospinning. The *in vitro* dissolution tests showed that the nanofibers could provide an immediate release of 42.3% of the drug followed by a sustained release over 10 h of the remaining drug [66]. Other researchers have used simple sequential electrospinning to create a triple layered nanofiber mesh with biphasic drug release behavior. The mesh was composed of zein and polyvinylpyrrolidone as the top/bottom and middle layers, respectively. Ketoprofen was used as a model drug, and polyvinylpyrrolidone was blended with graphene oxide to improve the drug release functionality of the nanofiber as well as its mechanical properties. The *in vitro* release tests demonstrated time-regulated biphasic drug release [67]. In another study, gelatin-ciprofloxacin nanofibers containing various amounts of ciprofloxacin were fabricated on the surface of Mg-Ca alloy *via* an electrospinning process. Prolonged drug release was attained from gelatin-ciprofloxacin nanofibers coating along with initial rapid drug release of around 20–22% during 12 h, followed by a slow release stage that can effectively control the infection [68]. Moreover, resveratrol (a promising natural substance for periodontal disease treatment due to its anti-inflammatory and antioxidative effects) was successfully incorporated into polycaprolactone-nanofibers and enabled a biphasic-release kinetic pattern [69]. In a recent study, it was demonstrated that the production of core-shell fibers via modified coaxial electrospinning achieved controlled release of ampicillin-loaded polycaprolactone nanofibers covered by a polycaprolactone shield. The *in vitro* release studies showed that the drug release kinetics of core-shell products is closer to zero-order kinetics, while the drug release kinetics of single electrospinning of the core resulted with burst release [70]. Scientists have also used piroxicam as a low-dose, poorly soluble drug and hydroxypropyl methylcellulose as an amorphous-state stabilizing carrier polymer in nanofibers to produce biphasic-release drug delivery systems [71].

Dual drug delivery systems have also been successfully developed by researchers. In a recent study, aceclofenac/pantoprazole-loaded zein/Eudragit S 100 nanofibers were developed using a single nozzle electrospinning process. The *in vitro* release studies ensured the efficiency of the nanofibers in sustaining the release of both drugs up to 8 h, while the *in vivo* experiments confirmed that the co-administration of pantoprazole and aceclofenac reduced the gastrointestinal toxicity induced by nonsteroidal anti-inflammatory drugs [72].

#### **4. Conclusions**

The fabrication of electrospun ultrafine fiber meshes from biodegradable and biocompatible polymers has opened new horizons in the biomedical field. Electrospinning, being a simple, highly versatile, and robust technique for the production of fibers with diameters from submicron down to nanometer scale, could provide a useful method for the development of novel drug carriers capable of affecting the drugs' modified release. By careful selection of polymers, it is now possible to deliver drugs, with diverse stereoelectronic and physicochemical properties, in a required manner using electrospun nanofibers. *Mutatis mutandis*, in order to make further progress in the drug delivery field, it is necessary to identify ways that

will allow fabrication of nanofibers with the desired morphological and mechanical properties in a reproducible manner. Thus, organic solvent mixtures, drug content, and electrospinning parameters, which will influence nanofiber properties, such as morphology, applicability, and quality, are currently under intense investigation.

### **Conflict of interest**

The authors declare no conflict of interest.

### **Author details**

Marilena Vlachou\*, Angeliki Siamidi and Sotiria Kyriakou Department of Pharmacy, Division of Pharmaceutical Technology, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece

\*Address all correspondence to: vlachou@pharm.uoa.gr

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**47**

*Electrospinning and Drug Delivery*

**References**

*DOI: http://dx.doi.org/10.5772/intechopen.86181*

[1] Sunil CU, Shridhar NB, Jagadeesh SS, Ravikumar C. Nanofibers in drug delivery: An overview. World Journal of Pharmaceutical Research. 2015;**4**(8):2576-2594. ISSN: 2277-7105 oral drug delivery. Nanomedicine Journal. 2017;**4**(4):197-207. DOI: 10.22038/nmj.2017.04.001

10.1155/2013/789289

s10965-013-0158-9

03.024

S43575

[9] Pillay V, Dott C, Choonara YE, Tyagi C, Tomar L, Kumar P, et al. A review of the effect of processing variables on the fabrication of electrospun nanofibers for drug delivery applications. Journal of Nanomaterials. 2013;**2013**:1-22. DOI:

[10] Braghirolli DI, Steffens D, Pranke P. Electrospinning for regenerative medicine: A review of the main topics. Drug Discovery Today. 2014;**19**(6): 743-753. DOI: 10.1016/j.drudis.2014.

[11] Bae HS, Haider A, Selim KMK, Kang DY, Kim EJ, Kang IK. Fabrication of highly porous PMMA electrospun fibers and their application in the removal of phenol and iodine. Journal of Polymer Research. 2013;**20**(7):1-7. DOI: 10.1007/

[12] Haider S, Al-Zeghayer Y, Ahmed Ali F, Haider A, Mahmood A, Al-Masry W, et al. Highly aligned narrow diameter chitosan electrospun nanofibers. Journal of Polymer Research. 2013;**20**(4):1-11. DOI: 10.1007/s10965-013-0105-9

International Journal of Nanomedicine. 2013;**8**(1):2997-3017. DOI: 10.2147/IJN.

[14] Imani R, Yousefzadeh M, Nour S. Functional nanofiber for drug delivery applications. In: Barhoum A, Bechelany M, Makhlouf A, editors. Handbook of Nanofibers. Cham: Springer; 2018. pp. 1-55. DOI: 10.1007/978-3-319-42789-8\_34-1

[15] Tipduangta P, Belton P, Fábián L, Wang LY, Tang H, Eddleston M, et al.

[13] Zamani M, Prabhakaran PM, Ramakrishna S. Advances in drug delivery via electrospun and electrosprayed nanomaterials.

[2] Sujitha R, Moin A, Gowda DV, Jigyasa V, Santhosh TR, Osmani RAM. Nanofibers: The newfangled loom in drug delivery and therapeutics. Indo American Journal of Pharmaceutical Research. 2016;**6**(03):4690-4697. ISSN: 2231-6876

[3] Manuel CBJ, Jesus VGL, Aracely SM. Electrospinning for drug delivery systems: Drug incorporation techniques. In: Haider S, Haider A, editors. Electrospinning - Material, Techniques, and Biomedical Applications. London: IntechOpen; 2016.

pp. 141-155. DOI: 10.5772/65939

[4] Haider A, Haider S, Kang IK. A comprehensive review summarizing the effect of electrospinning parameters and potential applications of nanofibers in biomedical and biotechnology. Arabian Journal of Chemistry. 2018;**11**:1165-1188.

DOI: 10.1016/j.arabjc.2015.11.015

[6] Wang B, Wang Y, Yin T, Yu Q. Applications of electrospinning technique in drug delivery. Chemical Engineering Communications. 2010;**197**(10):1315-1338. DOI: 10.1080/00986441003625997

[7] Weng L, Xie J. Smart electrospun nanofibers for controlled drug release: Recent advances and new perspectives. Current Pharmaceutical Design. 2015;**21**(15):1944-1959. DOI: 10.2174/13

[8] Akhgari A, Shakib Z, Sanati A. A review on electrospun nanofibers for

81612821666150302151959

[5] Laudenslager MJ, Sigmund WM. Electrospinning. In: Bhushan B, editor. Encyclopedia of Nanotechnology. Springer: Dordrecht; 2012. pp. 769-775. DOI: 10.1007/978-90-481-9751-4\_357

### **References**

*Electrospinning and Electrospraying - Techniques and Applications*

The authors declare no conflict of interest.

will allow fabrication of nanofibers with the desired morphological and mechanical properties in a reproducible manner. Thus, organic solvent mixtures, drug content, and electrospinning parameters, which will influence nanofiber properties, such as morphology, applicability, and quality, are currently under intense investigation.

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Department of Pharmacy, Division of Pharmaceutical Technology, School of Health

Sciences, National and Kapodistrian University of Athens, Athens, Greece

**46**

**Author details**

**Conflict of interest**

provided the original work is properly cited.

Marilena Vlachou\*, Angeliki Siamidi and Sotiria Kyriakou

\*Address all correspondence to: vlachou@pharm.uoa.gr

[1] Sunil CU, Shridhar NB, Jagadeesh SS, Ravikumar C. Nanofibers in drug delivery: An overview. World Journal of Pharmaceutical Research. 2015;**4**(8):2576-2594. ISSN: 2277-7105

[2] Sujitha R, Moin A, Gowda DV, Jigyasa V, Santhosh TR, Osmani RAM. Nanofibers: The newfangled loom in drug delivery and therapeutics. Indo American Journal of Pharmaceutical Research. 2016;**6**(03):4690-4697. ISSN: 2231-6876

[3] Manuel CBJ, Jesus VGL, Aracely SM. Electrospinning for drug delivery systems: Drug incorporation techniques. In: Haider S, Haider A, editors. Electrospinning - Material, Techniques, and Biomedical Applications. London: IntechOpen; 2016. pp. 141-155. DOI: 10.5772/65939

[4] Haider A, Haider S, Kang IK. A comprehensive review summarizing the effect of electrospinning parameters and potential applications of nanofibers in biomedical and biotechnology. Arabian Journal of Chemistry. 2018;**11**:1165-1188. DOI: 10.1016/j.arabjc.2015.11.015

[5] Laudenslager MJ, Sigmund WM. Electrospinning. In: Bhushan B, editor. Encyclopedia of Nanotechnology. Springer: Dordrecht; 2012. pp. 769-775. DOI: 10.1007/978-90-481-9751-4\_357

[6] Wang B, Wang Y, Yin T, Yu Q. Applications of electrospinning technique in drug delivery. Chemical Engineering Communications. 2010;**197**(10):1315-1338. DOI: 10.1080/00986441003625997

[7] Weng L, Xie J. Smart electrospun nanofibers for controlled drug release: Recent advances and new perspectives. Current Pharmaceutical Design. 2015;**21**(15):1944-1959. DOI: 10.2174/13 81612821666150302151959

[8] Akhgari A, Shakib Z, Sanati A. A review on electrospun nanofibers for oral drug delivery. Nanomedicine Journal. 2017;**4**(4):197-207. DOI: 10.22038/nmj.2017.04.001

[9] Pillay V, Dott C, Choonara YE, Tyagi C, Tomar L, Kumar P, et al. A review of the effect of processing variables on the fabrication of electrospun nanofibers for drug delivery applications. Journal of Nanomaterials. 2013;**2013**:1-22. DOI: 10.1155/2013/789289

[10] Braghirolli DI, Steffens D, Pranke P. Electrospinning for regenerative medicine: A review of the main topics. Drug Discovery Today. 2014;**19**(6): 743-753. DOI: 10.1016/j.drudis.2014. 03.024

[11] Bae HS, Haider A, Selim KMK, Kang DY, Kim EJ, Kang IK. Fabrication of highly porous PMMA electrospun fibers and their application in the removal of phenol and iodine. Journal of Polymer Research. 2013;**20**(7):1-7. DOI: 10.1007/ s10965-013-0158-9

[12] Haider S, Al-Zeghayer Y, Ahmed Ali F, Haider A, Mahmood A, Al-Masry W, et al. Highly aligned narrow diameter chitosan electrospun nanofibers. Journal of Polymer Research. 2013;**20**(4):1-11. DOI: 10.1007/s10965-013-0105-9

[13] Zamani M, Prabhakaran PM, Ramakrishna S. Advances in drug delivery via electrospun and electrosprayed nanomaterials. International Journal of Nanomedicine. 2013;**8**(1):2997-3017. DOI: 10.2147/IJN. S43575

[14] Imani R, Yousefzadeh M, Nour S. Functional nanofiber for drug delivery applications. In: Barhoum A, Bechelany M, Makhlouf A, editors. Handbook of Nanofibers. Cham: Springer; 2018. pp. 1-55. DOI: 10.1007/978-3-319-42789-8\_34-1

[15] Tipduangta P, Belton P, Fábián L, Wang LY, Tang H, Eddleston M, et al. Electrospun polymer blend nanofibers for tunable drug delivery: The role of transformative phase separation on controlling the release rate. Molecular Pharmaceutics. 2016;**13**(1):25-39. DOI: 10.1021/acs.molpharmaceut.5b00359

[16] Ravi Kumar RMV. Handjournal of Polyester Drug Delivery Systems. 1st ed. Vol. 1. Boca Ratón, FL: CRC Press; 2016. pp. 1-738. ISBN: 9789814669658

[17] Volpato FZ, Almodovar J, Erickson K, Popat KC, Migliaresi C, Kipper MJ. Preservation of FGF-2 bioactivity using heparin-based nanoparticles, and their delivery from electrospun chitosan fibers. Acta Biomaterialia. 2012;**8**(4):1551-1559. DOI: 10.1016/j. actbio.2011.12.023

[18] Reda RI, Wen MM, El-Kamel AH. Ketoprofen-loaded Eudragit electrospun nanofibers for the treatment of oral mucositis. International Journal of Nanomedicine. 2017;**12**:2335-2351. DOI: 10.2147/IJN.S131253

[19] Ahmed FE, Lalia BS, Hashaikeh R. A review on electrospinning for membrane fabrication: Challenges and applications. Desalination. 2015;**356**: 15-30. DOI: 10.1016/j.desal.2014.09.033

[20] Costa LMM, Bretas RES, Gregorio R. Effect of solution concentration on the electrospray/electrospinning transition and on the crystalline phase of PVDF. Materials Sciences and Applications. 2010;**1**:247-252. DOI: 10.4236/msa.2010.14036

[21] Baumgarten PK. Electrostatic spinning of acrylic microfibers. Journal of Colloid and Interface Science. 1971;**36**(1):71-79. DOI: 10.1016/0021-9797(71)90241-4

[22] Zong X, Kim K, Fang D, Ran S, Hsiao BS, Chu B. Structure and process relationship of electrospun bioabsorbable nanofiber membranes. Polymer. 2002;**43**(16):4403-4412. DOI: 10.1016/S0032-3861(02)00275-6

[23] Fong H, Chun I, Reneker D. Beaded nanofibers formed during electrospinning. Polymer. 1999;**40**(16):4585-4592. DOI: 10.1016/ S0032-3861(99)00068-3

[24] Shamim Z, Saeed B, Amir T, Abo Saied R, Rogheih D. The effect of flow rate on morphology and deposition area of electrospun nylon 6 nanofiber. Journal of Engineered Fibers and Fabrics. 2012;**7**(4):42-49. DOI: 10.1177/155892501200700414

[25] Doshi J, Reneker DH. Electrospinning process and applications of electrospun fibers. Journal of Electrostatics. 1995;**35**(2-3):151-160. DOI: 10.1016/0304-3886(95)00041-8

[26] Sun B, Long YZ, Zhang HD, Li MM, Duvail JL, Jiang XY, et al. Advances in three-dimensional nanofibrous macrostructures via electrospinning. Progress in Polymer Science. 2014;**39**(5):862-890. DOI: 10.1016/j. progpolymsci.2013.06.002

[27] Hayati I, Bailey AI, Tadros TF. Investigations into the mechanisms of electrohydrodynamic spraying of liquids: I. Effect of electric field and the environment on pendant drops and factors affecting the formation of stable jets and atomization. Journal of Colloid and Interface Science. 1987;**117**(1):205-221. DOI: 10.1016/0021-9797(87)90185-8

[28] Cai S, Xu H, Jiang Q, Yang Y. Novel 3D electrospun scaffolds with fibers oriented randomly and evenly in three dimensions to closely mimic the unique architectures of extracellular matrices in soft tissues: Fabrication and mechanism study. Langmuir. 2013;**29**(7):2311-2318. DOI: 10.1021/la304414j

[29] Choi JS, Lee SW, Jeong L, Bae SH, Min BC, Youk JH, et al. Effect of organosoluble salts on the nanofibrous structure of electrospun

**49**

ma8052718

*Electrospinning and Drug Delivery*

poly(3-hydroxybutyrate-co-3 hydroxyvalerate). International Journal of Biological Macromolecules. 2004;**34**(4):249-256. DOI: 10.1016/j.

[30] Teo WE. Introduction to Electrospinning Parameters and Fiber Control. 1st ed. Singapore: ElectrospinTech; 2015. pp. 25-29

[31] Megelski S, Stephens JS, Bruce Chase D, Rabolt JF. Micro- and nanostructured surface morphology on electrospun polymer fibers. Macromolecules. 2002;**35**(22): 8456-8466. DOI: 10.1021/ma020444a

[32] Zhang C, Yuan X, Wu L, Han Y, Sheng J. Study on morphology of electrospun poly(vinyl alcohol) mats. European Polymer Journal. 2005;**41**(3):423-432. DOI: 10.1016/j.

eurpolymj.2004.10.027

[33] Sill TJ, von Recum HA. Electrospinning: Applications in drug delivery and tissue engineering. Biomaterials. 2008;**29**(13):1989-2006. DOI: 10.1016/j.biomaterials.2008.01.011

[34] Deitzel JM, Kleinmeyer J, Harris D, Beck Tan NC. The effect of processing variables on the morphology of electrospun nanofibers and textiles. Polymer. 2001;**42**(1):261-272. DOI: 10.1016/S0032-3861(00)00250-0

[35] Matabola KP, Moutloali RM. The influence of electrospinning parameters on the morphology and diameter of poly(vinyledene fluoride) nanofiberseffect of sodium chloride. Journal of Materials Science. 2013;**48**(16):5475.

[36] Huan S, Liu G, Han G, Cheng W, Fu Z, Wu Q, et al. Effect of experimental

mechanical and hydrophobic properties of electrospun polystyrene fibers. Materials. 2015;**8**(5):2718. DOI: 10.3390/

DOI: 10.1002/app.31396

parameters on morphological,

ijbiomac.2004.06.001

*DOI: http://dx.doi.org/10.5772/intechopen.86181*

[37] Pelipenko J, Kristl J, Jankovic' B, Baumgartner S, Kocbek P. The impact of relative humidity during electrospinning on the morphology and mechanical properties of nanofibers. International Journal of Pharmaceutics. 2013;**456**(1):125-134. DOI: 10.1016/j.

ijpharm.2013.07.078

10.17795/jjnpp-33613

ijpharm.2014.10.036

colsurfb.2012.10.016

ijpharm.2017.05.004

[38] Bhardwaj N, Kundu SC.

Electrospinning: A fascinating fiber fabrication technique. Biotechnology Advances. 2010;**28**(3):325-347. DOI: 10.1016/j.biotechadv.2010.01.004

[39] Akhgari A, Ghalambor Dezfuli A, Rezaei M, Kiarsi M, Abbaspour MR. The design and evaluation of a fast dissolving drug delivery system for loratadine using the electrospinning method. Jundishapur Journal of Natural Pharmaceutical Products. 2016;**11**(2):e33613. DOI:

[40] Illangakoon UE, Gill H, Shearman GC, Parhizkar M, Mahalingam S, Chatterton NP, et al. Fast dissolving paracetamol/caffeine nanofibers prepared by electrospinning.

International Journal of Pharmaceutics. 2014;**477**(1-2):369-379. DOI: 10.1016/j.

[41] Li X, Kanjwal MA, Lin L, Chronakis

IS. Electrospun polyvinylalcohol nanofibers as oral fast-dissolving delivery system of caffeine and riboflavin. Colloid Surface B. 2013;**103**:182-188. DOI: 10.1016/j.

[42] Nam S, Lee JJ, Lee SY, Jeong JY, Kang WS, Cho HJ. Angelica gigas Nakai extract-loaded fast-dissolving nanofiber based on poly(vinyl alcohol) and soluplus for oral cancer therapy. International Journal of Pharmaceutics. 2017;**526**(1-2):225-234. DOI: 10.1016/j.

[43] Poller B, Strachan C, Broadbent R, Walker GF. A minitablet formulation made from electrospun nanofibers.

#### *Electrospinning and Drug Delivery DOI: http://dx.doi.org/10.5772/intechopen.86181*

*Electrospinning and Electrospraying - Techniques and Applications*

[23] Fong H, Chun I, Reneker D. Beaded nanofibers formed during electrospinning. Polymer. 1999;**40**(16):4585-4592. DOI: 10.1016/

[24] Shamim Z, Saeed B, Amir T, Abo Saied R, Rogheih D. The effect of flow rate on morphology and deposition area of electrospun nylon 6 nanofiber. Journal of Engineered Fibers and Fabrics. 2012;**7**(4):42-49. DOI: 10.1177/155892501200700414

[26] Sun B, Long YZ, Zhang HD, Li MM, Duvail JL, Jiang XY, et al. Advances in three-dimensional nanofibrous macrostructures via electrospinning.

S0032-3861(99)00068-3

[25] Doshi J, Reneker DH. Electrospinning process and applications of electrospun fibers. Journal of Electrostatics. 1995;**35**(2-3):151-160. DOI: 10.1016/0304-3886(95)00041-8

Progress in Polymer Science. 2014;**39**(5):862-890. DOI: 10.1016/j.

[27] Hayati I, Bailey AI, Tadros TF. Investigations into the mechanisms of electrohydrodynamic spraying of liquids: I. Effect of electric field and the environment on pendant drops and factors affecting the formation of stable jets and atomization. Journal of Colloid and Interface Science. 1987;**117**(1):205-221. DOI: 10.1016/0021-9797(87)90185-8

[28] Cai S, Xu H, Jiang Q, Yang Y. Novel 3D electrospun scaffolds with fibers oriented randomly and evenly in three dimensions to closely mimic the unique architectures of extracellular matrices in soft tissues: Fabrication and mechanism study. Langmuir. 2013;**29**(7):2311-2318.

DOI: 10.1021/la304414j

[29] Choi JS, Lee SW, Jeong L, Bae SH, Min BC, Youk JH, et al. Effect of organosoluble salts on the nanofibrous structure of electrospun

progpolymsci.2013.06.002

Electrospun polymer blend nanofibers for tunable drug delivery: The role of transformative phase separation on controlling the release rate. Molecular Pharmaceutics. 2016;**13**(1):25-39. DOI: 10.1021/acs.molpharmaceut.5b00359

[16] Ravi Kumar RMV. Handjournal of Polyester Drug Delivery Systems. 1st ed. Vol. 1. Boca Ratón, FL: CRC Press; 2016.

[17] Volpato FZ, Almodovar J, Erickson K, Popat KC, Migliaresi C, Kipper MJ. Preservation of FGF-2 bioactivity using heparin-based nanoparticles, and their delivery from electrospun chitosan fibers. Acta Biomaterialia. 2012;**8**(4):1551-1559. DOI: 10.1016/j.

[18] Reda RI, Wen MM, El-Kamel AH. Ketoprofen-loaded Eudragit electrospun nanofibers for the treatment of oral mucositis. International Journal of Nanomedicine. 2017;**12**:2335-2351. DOI:

[19] Ahmed FE, Lalia BS, Hashaikeh R. A review on electrospinning for membrane fabrication: Challenges and applications. Desalination. 2015;**356**: 15-30. DOI: 10.1016/j.desal.2014.09.033

[20] Costa LMM, Bretas RES, Gregorio R. Effect of solution concentration on the electrospray/electrospinning transition and on the crystalline phase of PVDF. Materials Sciences and Applications. 2010;**1**:247-252. DOI:

pp. 1-738. ISBN: 9789814669658

actbio.2011.12.023

10.2147/IJN.S131253

10.4236/msa.2010.14036

[21] Baumgarten PK. Electrostatic spinning of acrylic microfibers. Journal of Colloid and Interface Science. 1971;**36**(1):71-79. DOI: 10.1016/0021-9797(71)90241-4

[22] Zong X, Kim K, Fang D, Ran S, Hsiao BS, Chu B. Structure and process relationship of electrospun bioabsorbable nanofiber membranes. Polymer. 2002;**43**(16):4403-4412. DOI: 10.1016/S0032-3861(02)00275-6

**48**

poly(3-hydroxybutyrate-co-3 hydroxyvalerate). International Journal of Biological Macromolecules. 2004;**34**(4):249-256. DOI: 10.1016/j. ijbiomac.2004.06.001

[30] Teo WE. Introduction to Electrospinning Parameters and Fiber Control. 1st ed. Singapore: ElectrospinTech; 2015. pp. 25-29

[31] Megelski S, Stephens JS, Bruce Chase D, Rabolt JF. Micro- and nanostructured surface morphology on electrospun polymer fibers. Macromolecules. 2002;**35**(22): 8456-8466. DOI: 10.1021/ma020444a

[32] Zhang C, Yuan X, Wu L, Han Y, Sheng J. Study on morphology of electrospun poly(vinyl alcohol) mats. European Polymer Journal. 2005;**41**(3):423-432. DOI: 10.1016/j. eurpolymj.2004.10.027

[33] Sill TJ, von Recum HA. Electrospinning: Applications in drug delivery and tissue engineering. Biomaterials. 2008;**29**(13):1989-2006. DOI: 10.1016/j.biomaterials.2008.01.011

[34] Deitzel JM, Kleinmeyer J, Harris D, Beck Tan NC. The effect of processing variables on the morphology of electrospun nanofibers and textiles. Polymer. 2001;**42**(1):261-272. DOI: 10.1016/S0032-3861(00)00250-0

[35] Matabola KP, Moutloali RM. The influence of electrospinning parameters on the morphology and diameter of poly(vinyledene fluoride) nanofiberseffect of sodium chloride. Journal of Materials Science. 2013;**48**(16):5475. DOI: 10.1002/app.31396

[36] Huan S, Liu G, Han G, Cheng W, Fu Z, Wu Q, et al. Effect of experimental parameters on morphological, mechanical and hydrophobic properties of electrospun polystyrene fibers. Materials. 2015;**8**(5):2718. DOI: 10.3390/ ma8052718

[37] Pelipenko J, Kristl J, Jankovic' B, Baumgartner S, Kocbek P. The impact of relative humidity during electrospinning on the morphology and mechanical properties of nanofibers. International Journal of Pharmaceutics. 2013;**456**(1):125-134. DOI: 10.1016/j. ijpharm.2013.07.078

[38] Bhardwaj N, Kundu SC. Electrospinning: A fascinating fiber fabrication technique. Biotechnology Advances. 2010;**28**(3):325-347. DOI: 10.1016/j.biotechadv.2010.01.004

[39] Akhgari A, Ghalambor Dezfuli A, Rezaei M, Kiarsi M, Abbaspour MR. The design and evaluation of a fast dissolving drug delivery system for loratadine using the electrospinning method. Jundishapur Journal of Natural Pharmaceutical Products. 2016;**11**(2):e33613. DOI: 10.17795/jjnpp-33613

[40] Illangakoon UE, Gill H, Shearman GC, Parhizkar M, Mahalingam S, Chatterton NP, et al. Fast dissolving paracetamol/caffeine nanofibers prepared by electrospinning. International Journal of Pharmaceutics. 2014;**477**(1-2):369-379. DOI: 10.1016/j. ijpharm.2014.10.036

[41] Li X, Kanjwal MA, Lin L, Chronakis IS. Electrospun polyvinylalcohol nanofibers as oral fast-dissolving delivery system of caffeine and riboflavin. Colloid Surface B. 2013;**103**:182-188. DOI: 10.1016/j. colsurfb.2012.10.016

[42] Nam S, Lee JJ, Lee SY, Jeong JY, Kang WS, Cho HJ. Angelica gigas Nakai extract-loaded fast-dissolving nanofiber based on poly(vinyl alcohol) and soluplus for oral cancer therapy. International Journal of Pharmaceutics. 2017;**526**(1-2):225-234. DOI: 10.1016/j. ijpharm.2017.05.004

[43] Poller B, Strachan C, Broadbent R, Walker GF. A minitablet formulation made from electrospun nanofibers.

European Journal of Pharmaceutics and Biopharmaceutics. 2017;**114**:213-220. DOI: 10.1016/j.ejpb.2017.01.022

[44] Samprasit W, Akkaramongkolporn P, Ngawhirunpat T, Rojanarata T, Kaomongkolgit R, Opanasopit P. Fast releasing oral electrospun PVP/ CD nanofiber mats of taste-masked meloxicam. International Journal of Pharmaceutics. 2015;**487**(1-2):213-222. DOI: 10.1016/j.ijpharm.2015.04.044

[45] Sipos E, Szabo ZI, Redai E, Szabo P, Sebe I, Zelko R. Preparation and characterization of nanofibrous sheets for enhanced oral dissolution of nebivolol hydrochloride. Journal of Pharmaceutical and Biomedical Analysis. 2016;**109**:224-228. DOI: 10.1016/j.jpba.2016.07.004

[46] Yu DG, Shen XX, Branford-White C, White K, Zhu LM, Bligh SWA. Oral fast dissolving drug delivery membranes prepared from electrospun PVP ultrafine fibers. Nanotechnology. 2009;**20**:055104. DOI: 10.1088/0957-4484/20/5/055104

[47] Kabay G, Meydan AE, Can GK, Demirci C, Mutlu M. Controlled release of a hydrophilic drug from electrospun amyloid-like protein blend nanofibers. Materials Science and Engineering: C. 2017;**81**:271-279. DOI: 10.1016/j. msec.2017.08.003

[48] Kenawy ER, Bowlin GL, Mansfield K, Layman J, Simpson DG, Sanders EH, et al. Release of tetracycline hydrochloride from electrospun poly(ethylene-covinylacetate), poly(lactic acid), and a blend. Journal of Controlled Release. 2002;**81**(1-2):57-64. DOI: 10.1016/S0168-3659(02)00041-X

[49] Sun XZ, Williams GR, Hou XX, Zhu LM. Electrospun curcuminloaded fibers with potential biomedica applications. Carbohydrate Polymers. 2013;**94**(1):147-153. DOI: 10.1016/j. carbpol.2012.12.064

[50] Laha A, Sharma CS, Majumdar S. Sustained drug release from multilayered sequentially crosslinked electrospun gelatin nanofiber mesh. Materials Science and Engineering: C. 2017;**76**:782-786. DOI: 10.1016/j. msec.2017.03.110

[51] Vlachou M, Kikionis S, Siamidi A, Tragou K, Kapoti S, Ioannou E, et al. Fabrication and characterization of electrospun Nanofibers for the modified release of the Chronobiotic hormone melatonin. Current Drug Delivery. 2019;**16**(1):79-85. DOI: 10.2174/1567201 815666180914095701

[52] Vlachou M, Kikionis S, Siamidi A, Tragou K, Ioannou E, Roussis V, et al. Modified in vitro release of melatonin loaded in nanofibrous electrospun mats incorporated into monolayered and three-layered tablets. Journal of Pharmaceutical Sciences. 2019;**108**(2):970-976. DOI: 10.1016/j. xphs.2018.09.035

[53] Illangakoon UE, Nazir T, Williams GR, Chatterton NP. Mebeverineloaded electrospun nanofibers: Physicochemical characterization and dissolution studies. Pharmaceutical Nanotechnology. 2014;**103**(1):283-292. DOI: 10.1002/jps.23759

[54] Laha A, Yadav S, Majumdar S, Sharma CS. In-vitro release study of hydrophobic drug using electrospun cross-linked gelatin nanofibers. Biochemical Engineering Journal. 2016;**105**:481-488. DOI: 10.1016/j. bej.2015.11.001

[55] Hamori M, Yoshimatsu S, Hukuchi Y, Shimizu Y, Fukushima K, Sugioka N, et al. Preparation and pharmaceutical evaluation of nano-fiber matrix supported drug delivery system using the solvent-based electrospinning method. International Journal of Pharmaceutics. 2014;**464** (1-2):243-251. DOI: 10.1016/j. ijpharm.2013.12.036

**51**

*Electrospinning and Drug Delivery*

biopha.2015.12.023

ijpharm.2011.01.058

*DOI: http://dx.doi.org/10.5772/intechopen.86181*

[56] Hamori M, Nagano K, Kakimoto S, Naruhashi K, Kiriyama A, Nishimura A, et al. Preparation and pharmaceutical evaluation of acetaminophen nano-fiber tablets: Application of a solvent-based electrospinning method for tableting. Biomedicine & Pharmacotherapy. 2016;**78**:14-22. DOI: 10.1016/j.

et al. Fabrication, physico-chemical, and pharmaceutical characterization of budesonide-loaded electrospun fibers for drug targeting to the colon. Journal of Pharmaceutical Sciences. 2015;**104**(11):3798-3803. DOI: 10.1002/

[63] Wen P, Feng K, Yang H, Huang X, Zong MH, Lou WY, et al. Electrospun core-shell structured nanofilm as a novel colon-specific delivery system for protein. Carbohydrate Polymers. 2017;**169**:157-166. DOI: 10.1016/j.

[64] Jiang J, Xie J, Ma B, Bartlett DE, Xu A, Wang CH. Mussel-inspired proteinmediated surface functionalization of electrospun nanofibers for pH-responsive drug delivery. Acta Biomaterialia. 2014;**10**(3):1324-1332. DOI: 10.1016/j.actbio.2013.11.012

[65] Yu DG, Wang X, Li XY, Chian W, Li Y, Liao YZ. Electrospun biphasic drug release polyvinylpyrrolidone/ethyl cellulose core/sheath nanofibers. Acta Biomaterialia. 2013;**9**(3):5665-5672. DOI: 10.1016/j.actbio.2012.10.021

[66] Jiang YN, Mo HY, Yu DG.

[67] Lee H, Xu X, Kharaghani D, Nishino M, Song KH, Lee JS, et al. Electrospun tri-layered zein/PVP-GO/ zein nanofiber mats for providing biphasic drug release profiles.

ijpharm.2017.08.081

International Journal of Pharmaceutics. 2017;**531**(1):101-107. DOI: 10.1016/j.

[68] Bakhsheshi-Rad HR, Hadisi Z, Hamzah E, Ismail AF, Aziz M, Kashefian M. Drug delivery and cytocompatibility of ciprofloxacin loaded gelatin nanofibers-coated

Electrospun drug-loaded core-sheath PVP/zein nanofibers for biphasic drug release. International Journal of Pharmaceutics. 2012;**438**(1-2):232-239. DOI: 10.1016/j.ijpharm.2012.08.053

jps.24587

carbpol.2017.03.082

[57] Shen X, Yu D, Zhu L, Branford-White C, White K, Chatterton NP. Electrospun diclofenac sodium loaded Eudragit® L 100-55 nanofibers for colon-targeted drug delivery. International Journal of Pharmaceutics. 2011;**408**(1-2):200-207. DOI: 10.1016/j.

[58] Wang X, Yu DG, Li XY, Bligh SWA, Williams GR. Electrospun medicated shellac nanofibers for colon-targeted drug delivery. International Journal of Pharmaceutics. 2015;**490**(1-2):384-390. DOI: 10.1016/j.ijpharm.2015.05.077

[59] Akhgari A, Heshmati Z, Afrasiabi Garekani H, Sadeghi F, Sabbagh A, Sharif Makhmalzadeh B, et al. Indomethacin electrospun nanofibers for colonic drug delivery: In vitro dissolution studies. Colloids and Surfaces B: Biointerfaces.

2017;**152**:29-35. DOI: 10.1016/j.

[61] Akhgari A, Rotubati MH. Preparation and evaluation of

DOI: 10.7508/nmj.2016.01.005

[62] Bruni G, Maggi L, Tammaro L, Canobbio A, Di Lorenzo R, D'Aniello S,

electrospun nanofibers containing pectin and time-dependent polymers aimed for colonic drug delivery of celecoxib. Nanomedicine Journal. 2016;**3**(1):43-48.

[60] Akhgari A, Heshmati Z, Sharif Makhmalzadeh B. Indomethacin electrospun nanofibers for colonic drug delivery: Preparation and characterization. Advanced Pharmaceutical Bulletin. 2013;**3**(1): 85-90. DOI: 10.5681/apb.2013.014

colsurfb.2016.12.035

#### *Electrospinning and Drug Delivery DOI: http://dx.doi.org/10.5772/intechopen.86181*

*Electrospinning and Electrospraying - Techniques and Applications*

[50] Laha A, Sharma CS, Majumdar S. Sustained drug release from multilayered sequentially crosslinked electrospun gelatin nanofiber mesh. Materials Science and Engineering: C. 2017;**76**:782-786. DOI: 10.1016/j.

[51] Vlachou M, Kikionis S, Siamidi A, Tragou K, Kapoti S, Ioannou E, et al. Fabrication and characterization of electrospun Nanofibers for the modified release of the Chronobiotic hormone melatonin. Current Drug Delivery. 2019;**16**(1):79-85. DOI: 10.2174/1567201

[52] Vlachou M, Kikionis S, Siamidi A, Tragou K, Ioannou E, Roussis V, et al. Modified in vitro release of melatonin loaded in nanofibrous electrospun mats incorporated into monolayered and three-layered tablets. Journal of Pharmaceutical Sciences. 2019;**108**(2):970-976. DOI: 10.1016/j.

[53] Illangakoon UE, Nazir T, Williams GR, Chatterton NP. Mebeverineloaded electrospun nanofibers: Physicochemical characterization and dissolution studies. Pharmaceutical Nanotechnology. 2014;**103**(1):283-292.

[54] Laha A, Yadav S, Majumdar S, Sharma CS. In-vitro release study of hydrophobic drug using electrospun cross-linked gelatin nanofibers. Biochemical Engineering Journal. 2016;**105**:481-488. DOI: 10.1016/j.

[55] Hamori M, Yoshimatsu S, Hukuchi Y, Shimizu Y, Fukushima K, Sugioka N, et al. Preparation and pharmaceutical evaluation of nano-fiber matrix supported drug delivery system using the solvent-based electrospinning method. International Journal of

msec.2017.03.110

815666180914095701

xphs.2018.09.035

DOI: 10.1002/jps.23759

bej.2015.11.001

Pharmaceutics. 2014;**464** (1-2):243-251. DOI: 10.1016/j.

ijpharm.2013.12.036

European Journal of Pharmaceutics and Biopharmaceutics. 2017;**114**:213-220. DOI: 10.1016/j.ejpb.2017.01.022

[44] Samprasit W, Akkaramongkolporn P, Ngawhirunpat T, Rojanarata T, Kaomongkolgit R, Opanasopit P. Fast releasing oral electrospun PVP/ CD nanofiber mats of taste-masked meloxicam. International Journal of Pharmaceutics. 2015;**487**(1-2):213-222. DOI: 10.1016/j.ijpharm.2015.04.044

[45] Sipos E, Szabo ZI, Redai E, Szabo P, Sebe I, Zelko R. Preparation and characterization of nanofibrous sheets for enhanced oral dissolution of nebivolol hydrochloride. Journal of Pharmaceutical and Biomedical Analysis. 2016;**109**:224-228. DOI: 10.1016/j.jpba.2016.07.004

[46] Yu DG, Shen XX, Branford-White C, White K, Zhu LM, Bligh SWA. Oral fast dissolving drug delivery membranes prepared from electrospun PVP ultrafine fibers. Nanotechnology. 2009;**20**:055104. DOI:

10.1088/0957-4484/20/5/055104

msec.2017.08.003

carbpol.2012.12.064

[47] Kabay G, Meydan AE, Can GK, Demirci C, Mutlu M. Controlled release of a hydrophilic drug from electrospun amyloid-like protein blend nanofibers. Materials Science and Engineering: C. 2017;**81**:271-279. DOI: 10.1016/j.

[48] Kenawy ER, Bowlin GL, Mansfield K, Layman J, Simpson DG, Sanders EH, et al. Release of tetracycline hydrochloride from electrospun poly(ethylene-covinylacetate),

poly(lactic acid), and a blend. Journal of Controlled Release. 2002;**81**(1-2):57-64. DOI: 10.1016/S0168-3659(02)00041-X

[49] Sun XZ, Williams GR, Hou XX, Zhu LM. Electrospun curcuminloaded fibers with potential biomedica applications. Carbohydrate Polymers. 2013;**94**(1):147-153. DOI: 10.1016/j.

**50**

[56] Hamori M, Nagano K, Kakimoto S, Naruhashi K, Kiriyama A, Nishimura A, et al. Preparation and pharmaceutical evaluation of acetaminophen nano-fiber tablets: Application of a solvent-based electrospinning method for tableting. Biomedicine & Pharmacotherapy. 2016;**78**:14-22. DOI: 10.1016/j. biopha.2015.12.023

[57] Shen X, Yu D, Zhu L, Branford-White C, White K, Chatterton NP. Electrospun diclofenac sodium loaded Eudragit® L 100-55 nanofibers for colon-targeted drug delivery. International Journal of Pharmaceutics. 2011;**408**(1-2):200-207. DOI: 10.1016/j. ijpharm.2011.01.058

[58] Wang X, Yu DG, Li XY, Bligh SWA, Williams GR. Electrospun medicated shellac nanofibers for colon-targeted drug delivery. International Journal of Pharmaceutics. 2015;**490**(1-2):384-390. DOI: 10.1016/j.ijpharm.2015.05.077

[59] Akhgari A, Heshmati Z, Afrasiabi Garekani H, Sadeghi F, Sabbagh A, Sharif Makhmalzadeh B, et al. Indomethacin electrospun nanofibers for colonic drug delivery: In vitro dissolution studies. Colloids and Surfaces B: Biointerfaces. 2017;**152**:29-35. DOI: 10.1016/j. colsurfb.2016.12.035

[60] Akhgari A, Heshmati Z, Sharif Makhmalzadeh B. Indomethacin electrospun nanofibers for colonic drug delivery: Preparation and characterization. Advanced Pharmaceutical Bulletin. 2013;**3**(1): 85-90. DOI: 10.5681/apb.2013.014

[61] Akhgari A, Rotubati MH. Preparation and evaluation of electrospun nanofibers containing pectin and time-dependent polymers aimed for colonic drug delivery of celecoxib. Nanomedicine Journal. 2016;**3**(1):43-48. DOI: 10.7508/nmj.2016.01.005

[62] Bruni G, Maggi L, Tammaro L, Canobbio A, Di Lorenzo R, D'Aniello S, et al. Fabrication, physico-chemical, and pharmaceutical characterization of budesonide-loaded electrospun fibers for drug targeting to the colon. Journal of Pharmaceutical Sciences. 2015;**104**(11):3798-3803. DOI: 10.1002/ jps.24587

[63] Wen P, Feng K, Yang H, Huang X, Zong MH, Lou WY, et al. Electrospun core-shell structured nanofilm as a novel colon-specific delivery system for protein. Carbohydrate Polymers. 2017;**169**:157-166. DOI: 10.1016/j. carbpol.2017.03.082

[64] Jiang J, Xie J, Ma B, Bartlett DE, Xu A, Wang CH. Mussel-inspired proteinmediated surface functionalization of electrospun nanofibers for pH-responsive drug delivery. Acta Biomaterialia. 2014;**10**(3):1324-1332. DOI: 10.1016/j.actbio.2013.11.012

[65] Yu DG, Wang X, Li XY, Chian W, Li Y, Liao YZ. Electrospun biphasic drug release polyvinylpyrrolidone/ethyl cellulose core/sheath nanofibers. Acta Biomaterialia. 2013;**9**(3):5665-5672. DOI: 10.1016/j.actbio.2012.10.021

[66] Jiang YN, Mo HY, Yu DG. Electrospun drug-loaded core-sheath PVP/zein nanofibers for biphasic drug release. International Journal of Pharmaceutics. 2012;**438**(1-2):232-239. DOI: 10.1016/j.ijpharm.2012.08.053

[67] Lee H, Xu X, Kharaghani D, Nishino M, Song KH, Lee JS, et al. Electrospun tri-layered zein/PVP-GO/ zein nanofiber mats for providing biphasic drug release profiles. International Journal of Pharmaceutics. 2017;**531**(1):101-107. DOI: 10.1016/j. ijpharm.2017.08.081

[68] Bakhsheshi-Rad HR, Hadisi Z, Hamzah E, Ismail AF, Aziz M, Kashefian M. Drug delivery and cytocompatibility of ciprofloxacin loaded gelatin nanofibers-coated

Mg alloy. Materials Letters. 2017;**207**: 179-182. DOI: 10.1016/j.matlet.2017. 07.072

[69] Zupančič S, Baumgartner S, Lavrič Z, Petelin M, Kristl J. Local delivery of resveratrol using polycaprolactone nanofibers for treatment of periodontal disease. Journal of Drug Delivery Science and Technology. 2015;**30**: 408-416. DOI: 10.1016/j.jddst.2015. 07.009

[70] Sultanova Z, Kaleli G, Kabay G, Mutlu M. Controlled release of a hydrophilic drug from coaxially electrospun polycaprolactone nanofibers. International Journal of Pharmaceutics. 2016;**505**(1-2):133-138. DOI: 10.1016/j.ijpharm.2016.03.032

[71] Paaver U, Heinamaki J, Laidmae I, Lust A, Kozlova J, Sillaste E, et al. Electrospun nanofibers as a potential controlled-release solid dispersion system for poorly water-soluble drugs. International Journal of Pharmaceutics. 2015;**479**(1):252-260. DOI: 10.1016/j. ijpharm.2014.12.024

[72] Karthikeyan K, Guhathakarta S, Rajaram R, Korrapati PS. Electrospun zein/eudragit nanofibers based dual drug delivery system for the simultaneous delivery of aceclofenac and pantoprazole. International Journal of Pharmaceutics. 2012;**438**(1-2): 117-122. DOI: 10.1016/j.ijpharm.2012. 07.075

**53**

**Chapter 3**

**Abstract**

catalysis

**1. Introduction**

Composites

Preparation, Characterization,

Carbon Nanofibers and Its

*Mayakrishnan Gopiraman and Ick Soo Kim*

and Applications of Electrospun

Carbon nanofibers (CNFs) and its composites have gained vast attention due to its exceptional chemical and textural properties. So far, various multifunctional carbon nanofibers and its composites are developed with highly unique and tunable morphology. In this chapter, we reviewed unique fabrication methods that are recently reported and its characterization techniques such as SEM, FE-SEM, TEM, WAXD, XPS, AFM, and Raman. In addition, catalytic, energy, and environmental applications of carbon nanofiber composites (metals and/or metal oxide nanoparticles incorporated and/or decorated hybrid carbon nanofibers) are discussed. Preparation and characterization of electrospun carbon nanofiber composites and its applications in catalysis and energy storage are the main focus of this chapter.

**Keywords:** electrospinning, carbon nanofibers, hollow structures, composites,

Carbon nanofibers have received growing interests due to their unique chemical and physical properties, depending upon their size, surface area, and shape [1, 2]. Indeed the attractive structural, electrical, and mechanical properties of carbon nanotubes (CNTs) make it an ideal supporting material for various applications. Particularly, the CNTs can be used as an efficient support for the decoration of catalytic active materials. Carbon nanofibers (CNFs) also have the similar physicochemical properties to CNTs and the diameter varying from some tens of nanometers to 500 nm [3] and are also suitable to be used as catalyst support. Electrospinning is a very simple but powerful method for the fabrication of high-quality carbon nanofibers [4]. In general, the CNFs with sub-micrometer diameters as well as some tens of nanometers to 500 nm are prepared by carbonization of electrospun polymer nanofibers under inert atmosphere at high temperature [5]. Undoubtedly, polyacrylonitrile (PAN) is a well-known and efficient precursor for the fabrication of carbon fibers [6]; therefore, several attempts were made to prepare the electrospun-derived carbon nanofibers from PAN [7]. Several approaches, including wet-chemical synthesis [8, 9], electrodeposition [10, 11], and dry synthesis [12–20], are developed to obtain various multifunctional active materials loaded with carbon nanocomposites. By using these techniques, various types of metal or metal oxide nanoparticles (NPs), such as Au,

#### **Chapter 3**

*Electrospinning and Electrospraying - Techniques and Applications*

Mg alloy. Materials Letters. 2017;**207**: 179-182. DOI: 10.1016/j.matlet.2017.

[69] Zupančič S, Baumgartner S, Lavrič Z, Petelin M, Kristl J. Local delivery of resveratrol using polycaprolactone nanofibers for treatment of periodontal disease. Journal of Drug Delivery Science and Technology. 2015;**30**: 408-416. DOI: 10.1016/j.jddst.2015.

[70] Sultanova Z, Kaleli G, Kabay G, Mutlu M. Controlled release of a hydrophilic drug from coaxially electrospun polycaprolactone nanofibers. International Journal of Pharmaceutics. 2016;**505**(1-2):133-138. DOI: 10.1016/j.ijpharm.2016.03.032

[71] Paaver U, Heinamaki J, Laidmae I, Lust A, Kozlova J, Sillaste E, et al. Electrospun nanofibers as a potential controlled-release solid dispersion system for poorly water-soluble drugs. International Journal of Pharmaceutics. 2015;**479**(1):252-260. DOI: 10.1016/j.

[72] Karthikeyan K, Guhathakarta S, Rajaram R, Korrapati PS. Electrospun zein/eudragit nanofibers based dual drug delivery system for the simultaneous delivery of aceclofenac and pantoprazole. International Journal of Pharmaceutics. 2012;**438**(1-2): 117-122. DOI: 10.1016/j.ijpharm.2012.

ijpharm.2014.12.024

07.072

07.009

**52**

07.075

## Preparation, Characterization, and Applications of Electrospun Carbon Nanofibers and Its Composites

*Mayakrishnan Gopiraman and Ick Soo Kim*

### **Abstract**

Carbon nanofibers (CNFs) and its composites have gained vast attention due to its exceptional chemical and textural properties. So far, various multifunctional carbon nanofibers and its composites are developed with highly unique and tunable morphology. In this chapter, we reviewed unique fabrication methods that are recently reported and its characterization techniques such as SEM, FE-SEM, TEM, WAXD, XPS, AFM, and Raman. In addition, catalytic, energy, and environmental applications of carbon nanofiber composites (metals and/or metal oxide nanoparticles incorporated and/or decorated hybrid carbon nanofibers) are discussed. Preparation and characterization of electrospun carbon nanofiber composites and its applications in catalysis and energy storage are the main focus of this chapter.

**Keywords:** electrospinning, carbon nanofibers, hollow structures, composites, catalysis

#### **1. Introduction**

Carbon nanofibers have received growing interests due to their unique chemical and physical properties, depending upon their size, surface area, and shape [1, 2]. Indeed the attractive structural, electrical, and mechanical properties of carbon nanotubes (CNTs) make it an ideal supporting material for various applications. Particularly, the CNTs can be used as an efficient support for the decoration of catalytic active materials. Carbon nanofibers (CNFs) also have the similar physicochemical properties to CNTs and the diameter varying from some tens of nanometers to 500 nm [3] and are also suitable to be used as catalyst support. Electrospinning is a very simple but powerful method for the fabrication of high-quality carbon nanofibers [4]. In general, the CNFs with sub-micrometer diameters as well as some tens of nanometers to 500 nm are prepared by carbonization of electrospun polymer nanofibers under inert atmosphere at high temperature [5]. Undoubtedly, polyacrylonitrile (PAN) is a well-known and efficient precursor for the fabrication of carbon fibers [6]; therefore, several attempts were made to prepare the electrospun-derived carbon nanofibers from PAN [7]. Several approaches, including wet-chemical synthesis [8, 9], electrodeposition [10, 11], and dry synthesis [12–20], are developed to obtain various multifunctional active materials loaded with carbon nanocomposites. By using these techniques, various types of metal or metal oxide nanoparticles (NPs), such as Au,

Co, Ru, Pt, Pd, Ag, Co, Rh, Ti and Cu, have been decorated or immobilized on/ into the carbon nanofibers. These metal NP-supported CNF nanocomposites have shown great promises in catalysis [21], fuel cells [22], and highly sensitive chemical/ biological sensing applications [23, 24]. In particularly, the CNF composites showed excellent results in various catalytic systems such as in photocatalytic activity [25, 26], water gas shift reactions (WGS) [27], enzyme immobilization or biocatalysts [28, 29], and direct oxidation of alcohols [30]. So far, TiO2-deposited CNFs have gained much attention in the photocatalytic reactions, and a considerable number of reports are available in the literature. Alike, Pd NP-supported CNFs are often preferred for the catalytic organic conversions such as hydrogenation reaction [31] and Heck coupling reaction [8]. It is proven that the CNFs are one of the highly suitable supports for the decoration of Pd NPs and the resultant Pd/CNF composite often demonstrated an enhanced catalytic activity [32]. In fact, the unique structure, high conductivity, huge surface area, and chemical inertness of CNFs often help to obtain high dispersion of metal nanoparticles on CNFs. Most of the Pd NP-supported CNFs showed better activity than the conventional Pd/C catalysts [8, 33].

In this chapter, we discussed the preparation and characterization of electrospun carbon fibers and its composites. The contributions of CNF composites in various catalytic systems (such as photocatalytic activity, water gas shift reactions (WGS), enzyme immobilization or biocatalysts, and direct oxidation of alcohols) are also discussed in detail.

### **2. Preparation and characterization of carbon nanofiber composites**

#### **2.1 Electrospun carbon nanofibers**

Electrospinning is a straightforward method to obtain the nanofibers. **Figure 1** shows the fundamental electrospinning setup and the list of important parameters to be controlled. The nanofibers can be produced by applying high voltage to a polymer solution which could create electrostatically repulsive force and an electric field between two electrodes, so that the nanofibers can be formed [34]. Obviously, the formation of nanofibers is highly dependent on the viscosity and electric conductivity of the polymeric fluids, humidity, and applied voltage [35]. To date,

**55**

*Preparation, Characterization, and Applications of Electrospun Carbon Nanofibers and Its…*

over 100 kinds of polymers have been employed to produce their nanofibers via electrospinning. However, a very limited number of polymers such as polyacrylonitrile (PAN), polyimide (PI), poly(vinyl alcohol) (PVA), poly(vinylidene fluoride) (PVDF), cellulose acetate, and pitch have been successfully used to obtain carbon nanofibers [36]. The carbon nanofibers are often characterized by various techniques. Scanning electron microscope (SEM) is one of the very common methods to characterize the CNFs. The surface morphology, particularly the fiber diameter, uniformity, and surface smoothness are often studied by SEM analysis. Alike, transmission electron microscopy (TEM) and atomic force microscopy (AFM) are also employed for the detail surface analysis. The crystalline and amorphous nature of the CNFs is often investigated by means of X-ray diffraction (XRD) analysis. Raman spectroscope is a very useful technique for the analysis of G-band and D-band of CNFs. X-ray photoemission spectroscopy (XPS) was also effectively used to analyze the CNFs. The specific surface area and textural properties such as pore volume and pore size of CNFs are evaluated by using the Brunauer-Emmett-Teller

Kim et al. [37] prepared CNFs via electrospinning by using PVA and DMF as precursor and solvent, respectively. In a typical preparation method, PVA was dissolved in DMF and the polymer mixture was electrospun. In the first step, the resultant nanofiber webs were oxidatively stabilized at 280°C under air flow (heating at 1°C/min). Then the stabilized nanofiber web was activated by steam resulting in activated carbon nanofibers. The stabilized nanofiber webs were heated at a rate of 5°C/min up to 700, 750, and 800°C and activated for 30 min by supplying 30 vol.% of steam in a carrier gas of N2. They confirmed that the resultant CNFs have well-developed mesopores and the CNFs demonstrated excellent specific

Kuzmenko and co-workers [38] prepared nitrogen-doped carbon nanofibrous

ammonium chloride provided the thermal stabilization of incompletely regenerated cellulose fibers. In a typical preparation, cellulose acetate solution was prepared in acetone/DMAc mixture which was subsequently electrospun. The voltage was 25 kV, distance between needle and collector was 25 cm, and the process was performed at temperature around 20 ± 2°C and relative humidity 45–60%. Aluminum foil was used for collecting the nanofibers. The prepared cellulose acetate nanofibers were deacetylated by using dilute NaOH solution. Then the regenerated cellulose webs were impregnated with NH4Cl by immersion in 0.3 M aqueous solution of NH4Cl for 24 h at 20 ± 2°C. The NH4Cl-treated regenerated cellulose samples were carbonized in a quartz tube furnace for general annealing in N2 flow (1 L/min) by heating up to 800°C with the heating rate of 5°C/min. **Figure 2** shows the SEM

Kim et al. [39] successfully prepared porous CNFs with hollow cores through the thermal treatment of electrospun copolymeric nanofiber webs. **Figure 3** shows the schematic diagram for producing porous CNFs with hollow cores. For the preparation of pores CNFs with hollow cores, PAN and poly(methyl methacrylate) (PMMA) polymers were chosen. The PAN is a widely used precursor for the preparation of CNFs, and the PMMA can be thermally decomposed at elevated temperatures. Dissolving these two polymers (PAN and PMMA) in a solvent would create phase separation [continuous phase (sea) changes into pore walls (or skeletons of nanofibers) and the discontinuous phase (islands) changes into many hollow pores], which results in the *sea-islands* feature. It is well known that

mats from regenerated cellulose impregnated with ammonium chloride. The

images of the CNFs synthesized from the regenerated cellulose [38].

**2.2 Porous carbon nanofibers with hollow cores**

*DOI: http://dx.doi.org/10.5772/intechopen.88317*

(BET) method.

capacitance (173 F/g at 10 mA/g).

*Scheme of fundamental setup for electrospinning and electrospinning parameters.*

*Preparation, Characterization, and Applications of Electrospun Carbon Nanofibers and Its… DOI: http://dx.doi.org/10.5772/intechopen.88317*

over 100 kinds of polymers have been employed to produce their nanofibers via electrospinning. However, a very limited number of polymers such as polyacrylonitrile (PAN), polyimide (PI), poly(vinyl alcohol) (PVA), poly(vinylidene fluoride) (PVDF), cellulose acetate, and pitch have been successfully used to obtain carbon nanofibers [36]. The carbon nanofibers are often characterized by various techniques. Scanning electron microscope (SEM) is one of the very common methods to characterize the CNFs. The surface morphology, particularly the fiber diameter, uniformity, and surface smoothness are often studied by SEM analysis. Alike, transmission electron microscopy (TEM) and atomic force microscopy (AFM) are also employed for the detail surface analysis. The crystalline and amorphous nature of the CNFs is often investigated by means of X-ray diffraction (XRD) analysis. Raman spectroscope is a very useful technique for the analysis of G-band and D-band of CNFs. X-ray photoemission spectroscopy (XPS) was also effectively used to analyze the CNFs. The specific surface area and textural properties such as pore volume and pore size of CNFs are evaluated by using the Brunauer-Emmett-Teller (BET) method.

Kim et al. [37] prepared CNFs via electrospinning by using PVA and DMF as precursor and solvent, respectively. In a typical preparation method, PVA was dissolved in DMF and the polymer mixture was electrospun. In the first step, the resultant nanofiber webs were oxidatively stabilized at 280°C under air flow (heating at 1°C/min). Then the stabilized nanofiber web was activated by steam resulting in activated carbon nanofibers. The stabilized nanofiber webs were heated at a rate of 5°C/min up to 700, 750, and 800°C and activated for 30 min by supplying 30 vol.% of steam in a carrier gas of N2. They confirmed that the resultant CNFs have well-developed mesopores and the CNFs demonstrated excellent specific capacitance (173 F/g at 10 mA/g).

Kuzmenko and co-workers [38] prepared nitrogen-doped carbon nanofibrous mats from regenerated cellulose impregnated with ammonium chloride. The ammonium chloride provided the thermal stabilization of incompletely regenerated cellulose fibers. In a typical preparation, cellulose acetate solution was prepared in acetone/DMAc mixture which was subsequently electrospun. The voltage was 25 kV, distance between needle and collector was 25 cm, and the process was performed at temperature around 20 ± 2°C and relative humidity 45–60%. Aluminum foil was used for collecting the nanofibers. The prepared cellulose acetate nanofibers were deacetylated by using dilute NaOH solution. Then the regenerated cellulose webs were impregnated with NH4Cl by immersion in 0.3 M aqueous solution of NH4Cl for 24 h at 20 ± 2°C. The NH4Cl-treated regenerated cellulose samples were carbonized in a quartz tube furnace for general annealing in N2 flow (1 L/min) by heating up to 800°C with the heating rate of 5°C/min. **Figure 2** shows the SEM images of the CNFs synthesized from the regenerated cellulose [38].

#### **2.2 Porous carbon nanofibers with hollow cores**

Kim et al. [39] successfully prepared porous CNFs with hollow cores through the thermal treatment of electrospun copolymeric nanofiber webs. **Figure 3** shows the schematic diagram for producing porous CNFs with hollow cores. For the preparation of pores CNFs with hollow cores, PAN and poly(methyl methacrylate) (PMMA) polymers were chosen. The PAN is a widely used precursor for the preparation of CNFs, and the PMMA can be thermally decomposed at elevated temperatures. Dissolving these two polymers (PAN and PMMA) in a solvent would create phase separation [continuous phase (sea) changes into pore walls (or skeletons of nanofibers) and the discontinuous phase (islands) changes into many hollow pores], which results in the *sea-islands* feature. It is well known that

*Electrospinning and Electrospraying - Techniques and Applications*

Co, Ru, Pt, Pd, Ag, Co, Rh, Ti and Cu, have been decorated or immobilized on/ into the carbon nanofibers. These metal NP-supported CNF nanocomposites have shown great promises in catalysis [21], fuel cells [22], and highly sensitive chemical/ biological sensing applications [23, 24]. In particularly, the CNF composites showed excellent results in various catalytic systems such as in photocatalytic activity [25, 26],

water gas shift reactions (WGS) [27], enzyme immobilization or biocatalysts [28, 29], and direct oxidation of alcohols [30]. So far, TiO2-deposited CNFs have gained much attention in the photocatalytic reactions, and a considerable number of reports are available in the literature. Alike, Pd NP-supported CNFs are often preferred for the catalytic organic conversions such as hydrogenation reaction [31] and Heck coupling reaction [8]. It is proven that the CNFs are one of the highly suitable supports for the decoration of Pd NPs and the resultant Pd/CNF composite often demonstrated an enhanced catalytic activity [32]. In fact, the unique structure, high conductivity, huge surface area, and chemical inertness of CNFs often help to obtain high dispersion of metal nanoparticles on CNFs. Most of the Pd NP-supported CNFs

showed better activity than the conventional Pd/C catalysts [8, 33].

*Scheme of fundamental setup for electrospinning and electrospinning parameters.*

discussed in detail.

**2.1 Electrospun carbon nanofibers**

In this chapter, we discussed the preparation and characterization of electrospun carbon fibers and its composites. The contributions of CNF composites in various catalytic systems (such as photocatalytic activity, water gas shift reactions (WGS), enzyme immobilization or biocatalysts, and direct oxidation of alcohols) are also

**2. Preparation and characterization of carbon nanofiber composites**

Electrospinning is a straightforward method to obtain the nanofibers. **Figure 1** shows the fundamental electrospinning setup and the list of important parameters to be controlled. The nanofibers can be produced by applying high voltage to a polymer solution which could create electrostatically repulsive force and an electric field between two electrodes, so that the nanofibers can be formed [34]. Obviously, the formation of nanofibers is highly dependent on the viscosity and electric conductivity of the polymeric fluids, humidity, and applied voltage [35]. To date,

**54**

**Figure 1.**

#### **Figure 2.**

*(a-f) SEM images of the CNFs synthesized from the differently regenerated cellulose with additional NH4Cl impregnation [38].*

#### **Figure 3.**

*Schematic diagram for the preparation of porous CNFs with hollow cores. (a) Preparation of stable polymer solutions from two separate phases; nanoscale phase separation occurs due to their different molecular weights; PMMA forms the discontinuous phase and PAN forms the continuous phase; (b) nanofiber formation (with two phases) by electrospinning; (c) removal of the PMMA phase at elevated temperatures [39].*

the low-surface-tension polymer (PAN) would occupy the continuous phase of the solution (*sea*), while the high-surface-tension polymer (PMMA) forms the discontinuous phase (*islands*). In fact the two separate phases are due to the intrinsic properties (e.g., interfacial tension, viscosity, elasticity) of the polymers [40]. The electrospinning technique was used to obtain the PAN/PMMA nanofibers containing two separate phases. The thermal treatment of PAN/PAMM nanofibers at over 1000°C would eventually form the porous carbon nanofibers with hollow cores. The complete removal of PMMA phase and the transformation continuous PAN phase would result in the formation of porous CNFs with hollow cores (**Figure 4**).

Highly flexible N- and O-containing porous ultrafine CNFs were prepared by Wei and co-workers [41]. The ultrafine porous CNFs were obtained by simply varying the PAN/PMMA ratios (10/0, 7:3, 5:5, and 3:7). Briefly, PAN/PMMA solutions with different ratios (10:0, 7:3, 5:5, and 3:7) are prepared in DMF. For better dispersion, the PAN/PMMA solution was sonicated followed by stirring at 60°C for 2h. The polymer blend was electrospun under an electric field of 9kV at a tip-to-collector distance of 15 cm. The resultant electrospun PAN/PMMA nanofibers were stabilized under air flow at 300°C with the heating rate of 1°C/min for 1h. Subsequently, the stabilized nanofibers were carbonized under N2 atmosphere at 900°C with heating rate of 5°C/min for 1h. It was proven that the increasing the ratio of PMMA would result in the formation of ultrafine CNFs. **Figure 5** shows the FE-SEM images of CNFs; CNFs, 7:3; CNFs, 5:5; and *u*-CNFs, 7:3. The FE-SEM images show that the morphology of CNFs is homogeneous, continuous, and a typical cylindrical shape.

**57**

467.57m2

**Figure 5.**

**Figure 4.**

/g and pore volume of 1.15 cm3

*PMMA, 7:3; (c) PAN/PMMA, 5:5; and (d) PAN/PMMA, 3:7 [41].*

*Preparation, Characterization, and Applications of Electrospun Carbon Nanofibers and Its…*

*(a–c) Cross-sectional TEM images of CNFs thermally treated at 2800°C [PAN:PMMA (a) 5:5, (b) 7:3, and (c) 9:1] and (d) TEM image of CNFs showing structurally developed core walls after thermal treatment [39].*

The FE-SEM images of CNFs, 7:3, and CNFs, 5:5, showed that the CNFs have several hollow cores along the fiber axis. Notably, the morphology of the u-CNFs (3:7) was completely changed. The morphology of CNFs (3:7) fibers was homogenous, continuous, and a cylindrical shape with an average diameter of ~50nm. In fact, the complete decomposition of PMMA during the thermal treatment is the main reason. The BET specific surface area of the u-CNFs-3,7 was determined to be

*FE-SEM images of electrospun PAN/PMMA nanofibers with different mixing ratios. (a) CNFs; (b) PAN/*

g<sup>−</sup><sup>1</sup>

and d) shows the TEM images of ultrathin micro-/mesoporous CNFs.

Chang et al. [42] introduced a novel technique of centrifuged-electrospinning for the preparation of ultrathin carbon fibers. **Figure 6** shows the preparation diagram of the ultrathin porous CNFs by centrifuged-electrospinning. In a typical procedure, PAN/PMMA polymer blend was prepared in DMF at different weight ratios of 80/20 (PAN80/PMMA20) and 10/90 (PAN10/PMMA90). The polymer blends were used for the preparation of PAN/PMMA nanofibers by centrifuged electrospinning. The centrifuged-electrospinning conditions were as follows: an applied positive voltage of 45 kV, a three-phase induction motor spinning at 4000 rpm, a syringe feed rate of 1.5 mL/min, and a stainless steel ring with a diameter of 50 cm as the collector. Finally, the resultant PAN/PMMA nanofibers were stabilized at 280°C for 2 h at a heating rate 0.5°C/min in air atmosphere and then carbonized at 800°C for 4 h under argon atmosphere at a heating rate of 5°C/min. **Figure 6** (b, c,

and an average pore size of 9.48nm.

*DOI: http://dx.doi.org/10.5772/intechopen.88317*

*Preparation, Characterization, and Applications of Electrospun Carbon Nanofibers and Its… DOI: http://dx.doi.org/10.5772/intechopen.88317*

#### **Figure 4.**

*Electrospinning and Electrospraying - Techniques and Applications*

the low-surface-tension polymer (PAN) would occupy the continuous phase of the solution (*sea*), while the high-surface-tension polymer (PMMA) forms the discontinuous phase (*islands*). In fact the two separate phases are due to the intrinsic properties (e.g., interfacial tension, viscosity, elasticity) of the polymers [40]. The electrospinning technique was used to obtain the PAN/PMMA nanofibers containing two separate phases. The thermal treatment of PAN/PAMM nanofibers at over 1000°C would eventually form the porous carbon nanofibers with hollow cores. The complete removal of PMMA phase and the transformation continuous PAN phase would result in the formation of porous CNFs with hollow cores (**Figure 4**).

*two phases) by electrospinning; (c) removal of the PMMA phase at elevated temperatures [39].*

*Schematic diagram for the preparation of porous CNFs with hollow cores. (a) Preparation of stable polymer solutions from two separate phases; nanoscale phase separation occurs due to their different molecular weights; PMMA forms the discontinuous phase and PAN forms the continuous phase; (b) nanofiber formation (with* 

*(a-f) SEM images of the CNFs synthesized from the differently regenerated cellulose with additional NH4Cl* 

Highly flexible N- and O-containing porous ultrafine CNFs were prepared by Wei and co-workers [41]. The ultrafine porous CNFs were obtained by simply varying the PAN/PMMA ratios (10/0, 7:3, 5:5, and 3:7). Briefly, PAN/PMMA solutions with different ratios (10:0, 7:3, 5:5, and 3:7) are prepared in DMF. For better dispersion, the PAN/PMMA solution was sonicated followed by stirring at 60°C for 2h. The polymer blend was electrospun under an electric field of 9kV at a tip-to-collector distance of 15 cm. The resultant electrospun PAN/PMMA nanofibers were stabilized under air flow at 300°C with the heating rate of 1°C/min for 1h. Subsequently, the stabilized nanofibers were carbonized under N2 atmosphere at 900°C with heating rate of 5°C/min for 1h. It was proven that the increasing the ratio of PMMA would result in the formation of ultrafine CNFs. **Figure 5** shows the FE-SEM images of CNFs; CNFs, 7:3; CNFs, 5:5; and *u*-CNFs, 7:3. The FE-SEM images show that the morphology of CNFs is homogeneous, continuous, and a typical cylindrical shape.

**56**

**Figure 2.**

**Figure 3.**

*impregnation [38].*

*(a–c) Cross-sectional TEM images of CNFs thermally treated at 2800°C [PAN:PMMA (a) 5:5, (b) 7:3, and (c) 9:1] and (d) TEM image of CNFs showing structurally developed core walls after thermal treatment [39].*

#### **Figure 5.**

*FE-SEM images of electrospun PAN/PMMA nanofibers with different mixing ratios. (a) CNFs; (b) PAN/ PMMA, 7:3; (c) PAN/PMMA, 5:5; and (d) PAN/PMMA, 3:7 [41].*

The FE-SEM images of CNFs, 7:3, and CNFs, 5:5, showed that the CNFs have several hollow cores along the fiber axis. Notably, the morphology of the u-CNFs (3:7) was completely changed. The morphology of CNFs (3:7) fibers was homogenous, continuous, and a cylindrical shape with an average diameter of ~50nm. In fact, the complete decomposition of PMMA during the thermal treatment is the main reason. The BET specific surface area of the u-CNFs-3,7 was determined to be 467.57m2 /g and pore volume of 1.15 cm3 g<sup>−</sup><sup>1</sup> and an average pore size of 9.48nm.

Chang et al. [42] introduced a novel technique of centrifuged-electrospinning for the preparation of ultrathin carbon fibers. **Figure 6** shows the preparation diagram of the ultrathin porous CNFs by centrifuged-electrospinning. In a typical procedure, PAN/PMMA polymer blend was prepared in DMF at different weight ratios of 80/20 (PAN80/PMMA20) and 10/90 (PAN10/PMMA90). The polymer blends were used for the preparation of PAN/PMMA nanofibers by centrifuged electrospinning. The centrifuged-electrospinning conditions were as follows: an applied positive voltage of 45 kV, a three-phase induction motor spinning at 4000 rpm, a syringe feed rate of 1.5 mL/min, and a stainless steel ring with a diameter of 50 cm as the collector. Finally, the resultant PAN/PMMA nanofibers were stabilized at 280°C for 2 h at a heating rate 0.5°C/min in air atmosphere and then carbonized at 800°C for 4 h under argon atmosphere at a heating rate of 5°C/min. **Figure 6** (b, c, and d) shows the TEM images of ultrathin micro-/mesoporous CNFs.

#### **Figure 6.**

*(a) Schematic diagram for the preparation of ultrathin micro-/mesoporous CNFs by centrifugedelectrospinning followed by carbonization and (b, c, and d) TEM images of ultrathin micro-/mesoporous CNFs [42].*

#### **2.3 Carbon nanofiber composites**

Recently, preparation of metal oxide-supported carbon nanofiber composites via electrospinning has been extensively studied. The carbon nanocomposites are used in various applications such as energy conversion and storage, capacitive deionization, catalysis, adsorption/separation, and in the field of biomedicine. In order to achieve higher activity, various synthetic routes were developed to achieve porous carbon nanofibers composites with high surface area and tunable pore size distribution. Most of the preparation methods involve carbonization process at elevated temperatures of typically above 1200°C. So far, various metal or metal oxide nanoparticle (Pd, Pt, Ti, Ag, Au, Cu, Ni, Zn, and Ru)-supported CNF nanocomposites were reported [21, 43].

Atchison et al. [44] prepared metal carbide-supported carbon nanocomposites through carbothermal reduction process. Zirconium carbide/carbon nanocomposite (ZrC/C), titanium carbide/carbon nanocomposite (TiC/C), and niobium carbide/ carbon nanocomposite (NbC/C) were prepared by electrospinning followed by carbothermal reduction at elevated temperatures. Cellulose acetate and PVP were used as precursor.

Chen et al. [45] prepared Pd nanoparticle-supported carbon nanofibers (Pd-NP/ CEPFs: Pd-NP/CEPFs) through the electrospinning process. Shortly, electrospinning solution was prepared by using 10 wt% PAN and 3.3 wt% Pd(OAc)2 in DMF. The electrospinning process was performed in an electric field of 30 kV and the tip-to-collector distance of 30 cm. Then the electrospun PAN/Pd(OAc)2 nanofiber involved three steps as follows: (1) 210°C annealing for 1 h under air flow for the oxidation of PAN, (2) heating up to 400°C at a rate of 5°C/min and annealing for 2 h in H2 and Ar mixture (H2/Ar = 1/3) atmosphere for the reduction of Pd2+, and (3) heating up to 550°C at a rate of 5°C/min and annealing for 1 h in Ar for the formation of metal nanoparticles on/in the carbonized nanofibers (**Figure 7**).

Zhang et al. [46] obtained AgNP-immobilized carbon nanocomposite by a two-step preparation: electrospinning followed by the hydrothermal growth of the AgNPs on the CNFs (**Figure 8**). In a typical procedure, the electrospinning solution

**59**

*Preparation, Characterization, and Applications of Electrospun Carbon Nanofibers and Its…*

*TEM images of Pd-NP/CENFs. (A) Lower magnification; (B) higher magnification [45].*

of PAN was prepared in DMF, and it was electrospun at an applied electric voltage of 10 kV. The PAN nanofibers were then stabilized under air flow at 270°C for 1 h and subsequently carbonized under N2 atmosphere at 1000°C for 1 h at the rate of 5°C/min. After the preparation of CNFs from PAN nanofibers, the CNFs were treated with HNO3, centrifuged, and washed with water for several times. Finally an aqueous mixture of glucose, Ag(NH3)2OH, and CNFs was stirred for 5 min. After being stirred for more than 5 min, the mixture was transferred into a Teflon-lined autoclave, and it was sealed in a stainless steel tank and heated at 180°C for 3 h.

*TEM images of sample (A) CNFs and (B) CNFs/AgNPs, (C) HRTEM images of CNFs/AgNPs, and (E) XRD* 

Yu and co-workers [47] prepared electrospun Ag/g-C3N4-loaded composite carbon nanofibers (Ag/g-C3N4/CNFs) through combing the electrospinning technology and carbonization treatment. The microstructure of Ag/g-C3N4/CNFs was

Ghouri et al. [48] achieved Co/CeO2-decorated carbon nanofibers (Co/CeO2/ CNFs) by calcination of electrospun nanofibers composed of cerium (III) acetate hydrate, cobalt (II) acetate tetrahydrate, and poly(vinyl alcohol) in nitrogen environment at 700°C. PVA was used as carbon source due to its high carbon content. In a typical preparation, CoAc and CeAc aqueous solutions were prepared in distilled water. The resultant aqueous solutions were mixed with PVA aqueous solution. After stirring for 6 h, the mixture was electrospun at high voltage of 22 kV using DC

Finally the AgNP-immobilized CNFs (Ag/CNFs) were obtained.

characterized by XRD, FE-SEM, EDS, TEM, and XPS.

*DOI: http://dx.doi.org/10.5772/intechopen.88317*

**Figure 7.**

**Figure 8.**

*patterns of CNFs/AgNPs and CNFs.*

*Preparation, Characterization, and Applications of Electrospun Carbon Nanofibers and Its… DOI: http://dx.doi.org/10.5772/intechopen.88317*

**Figure 7.**

*Electrospinning and Electrospraying - Techniques and Applications*

**2.3 Carbon nanofiber composites**

**Figure 6.**

*CNFs [42].*

composites were reported [21, 43].

used as precursor.

Recently, preparation of metal oxide-supported carbon nanofiber composites via electrospinning has been extensively studied. The carbon nanocomposites are used in various applications such as energy conversion and storage, capacitive deionization, catalysis, adsorption/separation, and in the field of biomedicine. In order to achieve higher activity, various synthetic routes were developed to achieve porous carbon nanofibers composites with high surface area and tunable pore size distribution. Most of the preparation methods involve carbonization process at elevated temperatures of typically above 1200°C. So far, various metal or metal oxide nanoparticle (Pd, Pt, Ti, Ag, Au, Cu, Ni, Zn, and Ru)-supported CNF nano-

*(a) Schematic diagram for the preparation of ultrathin micro-/mesoporous CNFs by centrifugedelectrospinning followed by carbonization and (b, c, and d) TEM images of ultrathin micro-/mesoporous* 

Atchison et al. [44] prepared metal carbide-supported carbon nanocomposites through carbothermal reduction process. Zirconium carbide/carbon nanocomposite (ZrC/C), titanium carbide/carbon nanocomposite (TiC/C), and niobium carbide/ carbon nanocomposite (NbC/C) were prepared by electrospinning followed by carbothermal reduction at elevated temperatures. Cellulose acetate and PVP were

Chen et al. [45] prepared Pd nanoparticle-supported carbon nanofibers (Pd-NP/

CEPFs: Pd-NP/CEPFs) through the electrospinning process. Shortly, electrospinning solution was prepared by using 10 wt% PAN and 3.3 wt% Pd(OAc)2 in DMF. The electrospinning process was performed in an electric field of 30 kV and the tip-to-collector distance of 30 cm. Then the electrospun PAN/Pd(OAc)2 nanofiber involved three steps as follows: (1) 210°C annealing for 1 h under air flow for the oxidation of PAN, (2) heating up to 400°C at a rate of 5°C/min and annealing for 2 h in H2 and Ar mixture (H2/Ar = 1/3) atmosphere for the reduction of Pd2+, and (3) heating up to 550°C at a rate of 5°C/min and annealing for 1 h in Ar for the formation of metal nanoparticles on/in the carbonized nanofibers (**Figure 7**). Zhang et al. [46] obtained AgNP-immobilized carbon nanocomposite by a two-step preparation: electrospinning followed by the hydrothermal growth of the AgNPs on the CNFs (**Figure 8**). In a typical procedure, the electrospinning solution

**58**

#### **Figure 8.**

*TEM images of sample (A) CNFs and (B) CNFs/AgNPs, (C) HRTEM images of CNFs/AgNPs, and (E) XRD patterns of CNFs/AgNPs and CNFs.*

of PAN was prepared in DMF, and it was electrospun at an applied electric voltage of 10 kV. The PAN nanofibers were then stabilized under air flow at 270°C for 1 h and subsequently carbonized under N2 atmosphere at 1000°C for 1 h at the rate of 5°C/min. After the preparation of CNFs from PAN nanofibers, the CNFs were treated with HNO3, centrifuged, and washed with water for several times. Finally an aqueous mixture of glucose, Ag(NH3)2OH, and CNFs was stirred for 5 min. After being stirred for more than 5 min, the mixture was transferred into a Teflon-lined autoclave, and it was sealed in a stainless steel tank and heated at 180°C for 3 h. Finally the AgNP-immobilized CNFs (Ag/CNFs) were obtained.

Yu and co-workers [47] prepared electrospun Ag/g-C3N4-loaded composite carbon nanofibers (Ag/g-C3N4/CNFs) through combing the electrospinning technology and carbonization treatment. The microstructure of Ag/g-C3N4/CNFs was characterized by XRD, FE-SEM, EDS, TEM, and XPS.

Ghouri et al. [48] achieved Co/CeO2-decorated carbon nanofibers (Co/CeO2/ CNFs) by calcination of electrospun nanofibers composed of cerium (III) acetate hydrate, cobalt (II) acetate tetrahydrate, and poly(vinyl alcohol) in nitrogen environment at 700°C. PVA was used as carbon source due to its high carbon content. In a typical preparation, CoAc and CeAc aqueous solutions were prepared in distilled water. The resultant aqueous solutions were mixed with PVA aqueous solution. After stirring for 6 h, the mixture was electrospun at high voltage of 22 kV using DC power supply at room temperature with 65% relative humidity. The tip-to-collector distance of 22 cm was fixed. Finally, the dried nanofiber mats were calcined at 700°C for 6 h in N2 flow with a heating rate of 2.0°C/min. The physicochemical properties of the Co/CeO2/CNFs were characterized by XRD, FE-SEM, EDS, TEM, XPS, and Raman.

The utilization of noble metals in green technologies has garnered an increasing level of research interest. Particularly, the Pt-based nanocomposites are often preferred as the anode because of their excellent performance in catalyzing the dehydrogenation of methanol. For example, Formo et al. [49] achieved Pt nanostructure-supported CNF nanofibers through electrospinning followed by calcination in air at 510°C for 6 h.

#### **3. Applications of carbon nanofiber composites**

Electrospun carbon nanofibers have proven to be efficient catalytic supports owing to the high porosity and large surface areas. The high porosity in a nonwoven mat of nanofibers enables direct growth of catalytic nanostructures. Till date, there are number of applications found for the electrospun carbon nanofibers and its composites.

#### **3.1 Carbon nanocomposites in organic transformations**

Owing to high surface area, porosity, stability, metal-support interaction, smaller particle size, and high dispersion in reaction medium, the metal nanoparticle-supported carbon nanocomposites demonstrated excellent activity in organic reactions. They can be highly reusable due its stability which is one of the hallmarks of the carbon nanocomposites.

Palladium-catalyzed Sonogashira coupling reaction is the most straightforward and powerful method used for the construction of C(sp2)–C(sp) bond, drugs, and polymeric materials [50]. The conventional protocols of the Sonogashira reactions are carried out in the homogeneous phase, using soluble palladium (Pd) composites such as Pd(PPh3)4, Pd(PPh3)2Cl2, and Pd(OAc)2 as catalysts in the presence of CuI as co-catalyst. Even with the high reaction rate and high turnover numbers, homogeneous catalysis has a number of disadvantages, in particular the lack of reuse of the catalyst. Chen et al. [45] developed Pd-supported CNF catalytic system for the Sonogashira reaction. **Figure 9** shows Pd-NP/CENF catalyzed Sonogashira reaction of iodobenzene and phenylacetylene in liquid phase. The catalyst showed superior catalytic activity toward the Sonogashira reaction. In addition, the catalyst was found to be highly reusable, at least for 10 runs without any significant loss in its catalytic activity.

Alike, electrospun Ag/g-C3N4-loaded composite carbon nanofibers (Ag/g-C3N4/ CNFs) were used for the conversion of 4-nitrophenol to 4-aminophenol and benzylamine to N-benzylbenzaldimine [44]. The Ag/g-C3N4/CNFs offered the significant advantages, such as low catalyst use, high activity, easy recycling, and excellent stability. In fact, the synergistic effect between catalytic activity of Ag nanoparticles

**Figure 9.**

*The Sonogashira reaction equation of iodobenzene and phenylacetylene in liquid phase catalyzed by Pd-NPsupported CNFs [45].*

**61**

**Figure 10.**

*with the CNF/AgNP composite nanofibers [46].*

*Preparation, Characterization, and Applications of Electrospun Carbon Nanofibers and Its…*

(NPs) and g-C3N4 and excellent adsorption capacity of carbon nanofibers are the

significant reactions in green chemistry [51]. It is well known that the nitrophenols are harmful to the environment, and therefore the US Environmental Protection Agency has listed it as 114th organic pollutant [52]. In recent days, catalytic conversion of nitrophenols to aminophenols is widely studied. In fact, the catalytic product, aminophenols, can be used as an excellent intermediate in synthesizing various drugs and reducing agent. The 4-nitrophenols are often employed as a photographic developer, corrosion inhibitor, anticorrosion lubricant, and hair-dyeing agent [53]. Although the reaction is very simple, greener, and most efficient, the reaction without metal catalysts is not achievable. To perform this reaction, various metal catalysts (based on graphene oxide, silica, alumina, activated carbon, CNTs, fullerenes, and so on) are developed and proven to be an excellent candidate for the reduction of 4-nitrophenols to 4-aminophenol. For example, RGO-ZnWO4-Fe3O4, AgNPs-rGO, PdNiP/RGO, and

Catalytic transformation of 4-nitrophenol to 4-aminophenol is one of the very

**3.2 Carbon nanocomposites in catalytic reduction of 4-nitrophenol**

NiNPs/silica are reported for the reduction of nitrophenol [20].

s<sup>−</sup><sup>1</sup>

without any significant loss in its catalytic activity.

**3.3 Carbon nanofiber composites in energy applications**

Carbon nanofibers/silver nanoparticle (CNFs/AgNPs) composite nanofibers were used for the reduction of 4-nitrophenol (4-NP) with NaBH4 [46]. The reaction was tracked by time-dependent UV-visible spectroscopy (**Figure 10**). It was found that the CNF/AgNP composite demonstrated an excellent catalytic activity in the reduction of 4-nitrophenol. The catalytic efficiency was found to be enhanced with the increasing of the content of silver on the CNF/AgNP catalyst. Reaction kinetic was studied for the CNF/AgNP reduction of 4-nitrophenol. It was reported that the

over CNF/AgNP catalyst. The excellent active might be attributed to the high surface areas of Ag NPs and synergistic effect on delivery of electrons between CNFs and AgNPs. The CNF/AgNP composite nanofibers can be easily recycled and reused

Due to the excellent properties such as high surface area, conductivity, and poros-

ity, the CNF-based nanocomposites are widely used for the energy applications. Without a doubt, the development of electrochemical energy storage systems (EES)

*Catalytic evolution of CNFs/AgNPs. (a) UV-vis absorption spectra during the reduction of 4-nitrophenol over CNFs/AgNPs; (b) ln(C/C0) and C/C0 vs. reaction time for the reduction of 4-nitrophenol, S0 = fresh CNFs, S1 = CNFs/AgNPs, and S2 = CNFs/AgNPs; (c) proposed mechanism of the catalytic reduction of 4-nitrophenol* 

was determined for the reduction of 4-nitrophenol

*DOI: http://dx.doi.org/10.5772/intechopen.88317*

rate constant of 6.2 × 10<sup>−</sup><sup>3</sup>

main reason for the excellent catalytic activity.

(NPs) and g-C3N4 and excellent adsorption capacity of carbon nanofibers are the main reason for the excellent catalytic activity.

#### **3.2 Carbon nanocomposites in catalytic reduction of 4-nitrophenol**

Catalytic transformation of 4-nitrophenol to 4-aminophenol is one of the very significant reactions in green chemistry [51]. It is well known that the nitrophenols are harmful to the environment, and therefore the US Environmental Protection Agency has listed it as 114th organic pollutant [52]. In recent days, catalytic conversion of nitrophenols to aminophenols is widely studied. In fact, the catalytic product, aminophenols, can be used as an excellent intermediate in synthesizing various drugs and reducing agent. The 4-nitrophenols are often employed as a photographic developer, corrosion inhibitor, anticorrosion lubricant, and hair-dyeing agent [53]. Although the reaction is very simple, greener, and most efficient, the reaction without metal catalysts is not achievable. To perform this reaction, various metal catalysts (based on graphene oxide, silica, alumina, activated carbon, CNTs, fullerenes, and so on) are developed and proven to be an excellent candidate for the reduction of 4-nitrophenols to 4-aminophenol. For example, RGO-ZnWO4-Fe3O4, AgNPs-rGO, PdNiP/RGO, and NiNPs/silica are reported for the reduction of nitrophenol [20].

Carbon nanofibers/silver nanoparticle (CNFs/AgNPs) composite nanofibers were used for the reduction of 4-nitrophenol (4-NP) with NaBH4 [46]. The reaction was tracked by time-dependent UV-visible spectroscopy (**Figure 10**). It was found that the CNF/AgNP composite demonstrated an excellent catalytic activity in the reduction of 4-nitrophenol. The catalytic efficiency was found to be enhanced with the increasing of the content of silver on the CNF/AgNP catalyst. Reaction kinetic was studied for the CNF/AgNP reduction of 4-nitrophenol. It was reported that the rate constant of 6.2 × 10<sup>−</sup><sup>3</sup> s<sup>−</sup><sup>1</sup> was determined for the reduction of 4-nitrophenol over CNF/AgNP catalyst. The excellent active might be attributed to the high surface areas of Ag NPs and synergistic effect on delivery of electrons between CNFs and AgNPs. The CNF/AgNP composite nanofibers can be easily recycled and reused without any significant loss in its catalytic activity.

#### **3.3 Carbon nanofiber composites in energy applications**

Due to the excellent properties such as high surface area, conductivity, and porosity, the CNF-based nanocomposites are widely used for the energy applications. Without a doubt, the development of electrochemical energy storage systems (EES)

#### **Figure 10.**

*Catalytic evolution of CNFs/AgNPs. (a) UV-vis absorption spectra during the reduction of 4-nitrophenol over CNFs/AgNPs; (b) ln(C/C0) and C/C0 vs. reaction time for the reduction of 4-nitrophenol, S0 = fresh CNFs, S1 = CNFs/AgNPs, and S2 = CNFs/AgNPs; (c) proposed mechanism of the catalytic reduction of 4-nitrophenol with the CNF/AgNP composite nanofibers [46].*

*Electrospinning and Electrospraying - Techniques and Applications*

**3. Applications of carbon nanofiber composites**

**3.1 Carbon nanocomposites in organic transformations**

XPS, and Raman.

composites.

tion in air at 510°C for 6 h.

of the carbon nanocomposites.

catalytic activity.

power supply at room temperature with 65% relative humidity. The tip-to-collector distance of 22 cm was fixed. Finally, the dried nanofiber mats were calcined at 700°C for 6 h in N2 flow with a heating rate of 2.0°C/min. The physicochemical properties of the Co/CeO2/CNFs were characterized by XRD, FE-SEM, EDS, TEM,

The utilization of noble metals in green technologies has garnered an increasing level of research interest. Particularly, the Pt-based nanocomposites are often preferred as the anode because of their excellent performance in catalyzing the dehydrogenation of methanol. For example, Formo et al. [49] achieved Pt nanostructure-supported CNF nanofibers through electrospinning followed by calcina-

Electrospun carbon nanofibers have proven to be efficient catalytic supports owing to the high porosity and large surface areas. The high porosity in a nonwoven mat of nanofibers enables direct growth of catalytic nanostructures. Till date, there are number of applications found for the electrospun carbon nanofibers and its

Owing to high surface area, porosity, stability, metal-support interaction, smaller particle size, and high dispersion in reaction medium, the metal nanoparticle-supported carbon nanocomposites demonstrated excellent activity in organic reactions. They can be highly reusable due its stability which is one of the hallmarks

Palladium-catalyzed Sonogashira coupling reaction is the most straightforward and powerful method used for the construction of C(sp2)–C(sp) bond, drugs, and polymeric materials [50]. The conventional protocols of the Sonogashira reactions are carried out in the homogeneous phase, using soluble palladium (Pd) composites such as Pd(PPh3)4, Pd(PPh3)2Cl2, and Pd(OAc)2 as catalysts in the presence of CuI as co-catalyst. Even with the high reaction rate and high turnover numbers, homogeneous catalysis has a number of disadvantages, in particular the lack of reuse of the catalyst. Chen et al. [45] developed Pd-supported CNF catalytic system for the Sonogashira reaction. **Figure 9** shows Pd-NP/CENF catalyzed Sonogashira reaction of iodobenzene and phenylacetylene in liquid phase. The catalyst showed superior catalytic activity toward the Sonogashira reaction. In addition, the catalyst was found to be highly reusable, at least for 10 runs without any significant loss in its

Alike, electrospun Ag/g-C3N4-loaded composite carbon nanofibers (Ag/g-C3N4/ CNFs) were used for the conversion of 4-nitrophenol to 4-aminophenol and benzylamine to N-benzylbenzaldimine [44]. The Ag/g-C3N4/CNFs offered the significant advantages, such as low catalyst use, high activity, easy recycling, and excellent stability. In fact, the synergistic effect between catalytic activity of Ag nanoparticles

*The Sonogashira reaction equation of iodobenzene and phenylacetylene in liquid phase catalyzed by Pd-NP-*

**60**

**Figure 9.**

*supported CNFs [45].*

**Figure 11.**

*(a) Cyclic voltammetry results for the ultrafine CNFs at different scan rates in 1.0 mol/L H2SO4 and; (b) specific capacitance for the u-CNFs (3:7) and CNFs at different scan rates in 1.0 mol/L H2SO4.*

is largely focused due to its vital demand for clean and sustainable energy. Mainly three types of devices are very important and most commercialized energy storage systems such as batteries, electrochemical capacitors (ECs), and fuel cells [54].

The ultrafine CNFs prepared via electrospinning of PAN/PMMA blend followed by thermal treatment in inert atmosphere were used as a flexible electrode material for the supercapacitor applications [41]. **Figure 11** shows the cyclic voltammetry results for the ultrafine CNFs at different scan rates in 1.0 mol/L H2SO4 and specific capacitance for the ultrafine CNFs at different scan rates in 1.0 mol/L H2SO4. The ultrafine CNFs demonstrated an enhanced specific capacitance of 86 F g<sup>−</sup><sup>1</sup> in 1 mol/L H2SO4. Being a flexible electrode material, this is the highest specific capacitance for the CNFs reported so far. The excellent specific capacitance of ultrafine CNFs is due to its unique properties. The results proved that the fiber diameter of ultrafine CNFs was about 50 nm. The XPS and Raman studies confirmed the presence of N and O in the form of various functional groups such as pyridinic, benzenoid amine, graphitic N, and N-oxides. High specific surface area of 467.57 m2 /g with an excellent pore volume (1.15 cm3 g<sup>−</sup><sup>1</sup> ) and pore size (9.48 nm) was determined for the ultrafine CNFs. The BET results confirmed the interconnected micro-/meso-/macropores on the surface of the ultrafine CNFs.

The Pt nanostructure-supported CNF nanocomposite was employed for the direct oxidation of methanol [49]. It was found that the Pt nanostructure-supported CNF nanocomposite showed better activity than the commercial Pt/C which may be due to the synergistic effect of the underlying anatase surface and the Pt nanostructures with well-defined facets. Alike, Co/CeO2-decorated carbon nanofibers were developed for the methanol oxidation [48]. The results showed that the electrocatalytic activity of the Co/CeO2-decorated carbon nanofibers toward methanol oxidation was excellent. Interestingly, the introduced catalyst revealed negative onset potential (50 mV vs. Ag/ AgCl) which is a superior value among the reported non-precious electrocatalyst.

#### **4. Conclusion**

Electrospinning is one of the simple and effective techniques for the fabrication of carbon nanofiber. Certainly, metal-supported carbon nanofibers demonstrated excellent activity in various applications such as catalysis, energy, and environmental. In this chapter, we have summarized the recent progress in the research on the preparation methods, characterization, and applications of electrospun carbon nanofibers and its composites.

**63**

**Author details**

Mayakrishnan Gopiraman1

Konkuk University, Seoul, South Korea

(ICCER), Shinshu University, Ueda, Japan

provided the original work is properly cited.

\*Address all correspondence to: kimicksoo@hotmail.com

and Ick Soo Kim2

\*

1 Department of Applied Bioscience, College of Life and Environmental Science,

2 Nano Fusion Technology Research Group, Division of Frontier Fibers, Institute for Fiber Engineering (IFES), Interdisciplinary Cluster for Cutting Edge Research

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

*Preparation, Characterization, and Applications of Electrospun Carbon Nanofibers and Its…*

*DOI: http://dx.doi.org/10.5772/intechopen.88317*

*Preparation, Characterization, and Applications of Electrospun Carbon Nanofibers and Its… DOI: http://dx.doi.org/10.5772/intechopen.88317*

#### **Author details**

*Electrospinning and Electrospraying - Techniques and Applications*

is largely focused due to its vital demand for clean and sustainable energy. Mainly three types of devices are very important and most commercialized energy storage systems such as batteries, electrochemical capacitors (ECs), and fuel cells [54].

*(a) Cyclic voltammetry results for the ultrafine CNFs at different scan rates in 1.0 mol/L H2SO4 and; (b) specific capacitance for the u-CNFs (3:7) and CNFs at different scan rates in 1.0 mol/L H2SO4.*

/g with an excellent pore volume (1.15 cm3

nected micro-/meso-/macropores on the surface of the ultrafine CNFs.

was determined for the ultrafine CNFs. The BET results confirmed the intercon-

The Pt nanostructure-supported CNF nanocomposite was employed for the direct oxidation of methanol [49]. It was found that the Pt nanostructure-supported CNF nanocomposite showed better activity than the commercial Pt/C which may be due to the synergistic effect of the underlying anatase surface and the Pt nanostructures with well-defined facets. Alike, Co/CeO2-decorated carbon nanofibers were developed for the methanol oxidation [48]. The results showed that the electrocatalytic activity of the Co/CeO2-decorated carbon nanofibers toward methanol oxidation was excellent. Interestingly, the introduced catalyst revealed negative onset potential (50 mV vs. Ag/ AgCl) which is a superior value among the reported non-precious electrocatalyst.

Electrospinning is one of the simple and effective techniques for the fabrication of carbon nanofiber. Certainly, metal-supported carbon nanofibers demonstrated excellent activity in various applications such as catalysis, energy, and environmental. In this chapter, we have summarized the recent progress in the research on the preparation methods, characterization, and applications of electrospun carbon

The ultrafine CNFs prepared via electrospinning of PAN/PMMA blend followed by thermal treatment in inert atmosphere were used as a flexible electrode material for the supercapacitor applications [41]. **Figure 11** shows the cyclic voltammetry results for the ultrafine CNFs at different scan rates in 1.0 mol/L H2SO4 and specific capacitance for the ultrafine CNFs at different scan rates in 1.0 mol/L H2SO4. The ultrafine CNFs demonstrated an enhanced specific capacitance of 86 F g<sup>−</sup><sup>1</sup> in 1 mol/L H2SO4. Being a flexible electrode material, this is the highest specific capacitance for the CNFs reported so far. The excellent specific capacitance of ultrafine CNFs is due to its unique properties. The results proved that the fiber diameter of ultrafine CNFs was about 50 nm. The XPS and Raman studies confirmed the presence of N and O in the form of various functional groups such as pyridinic, benzenoid amine, graphitic N, and N-oxides. High specific surface area

g<sup>−</sup><sup>1</sup>

) and pore size (9.48 nm)

**62**

of 467.57 m2

**Figure 11.**

**4. Conclusion**

nanofibers and its composites.

Mayakrishnan Gopiraman1 and Ick Soo Kim2 \*

1 Department of Applied Bioscience, College of Life and Environmental Science, Konkuk University, Seoul, South Korea

2 Nano Fusion Technology Research Group, Division of Frontier Fibers, Institute for Fiber Engineering (IFES), Interdisciplinary Cluster for Cutting Edge Research (ICCER), Shinshu University, Ueda, Japan

\*Address all correspondence to: kimicksoo@hotmail.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### **References**

[1] Burda C, Chen XB, Narayanan R, El-Sayed MA. Chemistry and properties of nanocrystals of different shapes. Chemical Reviews. 2005;**105**:1025-1102. DOI: 10.1021/cr030063a

[2] De Jong KP, Geus JW. Carbon nanofibers: Catalytic synthesis and applications. Catalysis Reviews. 2000;**42**:481-510. DOI: 10.1081/ CR-100101954

[3] Vamvakaki V, Tsagaraki K, Chaniotakis N. Carbon nanofiber-based glucose biosensor. Analytical Chemistry. 2006;**78**:5538-5542. DOI: 10.1021/ ac060551t

[4] Kim C, Yang KS, Kojima M, Yoshida K, Kim YJ, Kim YA, et al. Fabrication of electrospinning‐derived carbon nanofiber webs for the anode material of lithium‐ion secondary batteries. Advanced Functional Materials. 2006;**16**:2393-2397. DOI: 10.1002/ adfm.200500911

[5] Huang CB, Chen SL, Reneker DH, Lai CL, Hou HQ. High‐strength mats from electrospun poly(p‐phenylene biphenyltetracarboximide) nanofibers. Advanced Materials. 2006;**18**:668-671. DOI: 10.1002/adma.200501806

[6] Donnet JB, Bansal RC. Carbon Fibers. New York: Marcel Dekker; 1990

[7] Wang Y, Santiago-Aviles JJ. Conductivity measurement of electrospun PAN-based carbon nanofiber. Journal of Materials Science Letters. 2002;**21**:1055-1057

[8] Yoon B, Wai CM. Microemulsiontemplated synthesis of carbon nanotube-supported Pd and Rh nanoparticles for catalytic applications. Journal of the American Chemical Society. 2005;**127**(49):17174-17175. DOI: 10.1021/ja055530f

[9] Selvamani A, Babu CM, Ramkumar V, Sundaravel B. Reduced graphene oxide decorated Au nanoparticles as an efficient electrode for the determination of hydroquinone. Nano Progress. 2019;**1**:9-14

[10] Day TM, Unwin PR, Macpherson JV. Factors controlling the electrodeposition of metal nanoparticles on pristine single walled carbon nanotubes. Nano Letters. 2007;**7**:51-57. DOI: 10.1021/nl061974d

[11] Lin Z, Ji L, Zhang X. Electrodeposition of platinum nanoparticles onto carbon nanofibers for electrocatalytic oxidation of methanol. Materials Letters. 2009;**63**:2115-2118. DOI: 10.1016/j. matlet.2009.07.005

[12] Yuan G, Gopiraman M, Cha HJ, Soo HD, Chung IM, Kim IS. Interconnected ruthenium dioxide nanoparticles anchored on graphite oxide: Highly efficient candidate for solvent-free oxidative synthesis of imines. Journal of Industrial and Engineering Chemistry. 2017;**46**:279-288. DOI: 10.1016/j. jiec.2016.10.040

[13] Gopiraman M, Deng D, Babu SG, Hayashi T, Karvembu R, Kim IS. Sustainable and versatile CuO/ GNS nanocatalyst for highly efficient base free coupling reactions. ACS Sustainable Chemical Engineering. 2015;**3**:2478-2488. DOI: 10.1021/ acssuschemeng.5b00542

[14] Gopiraman M, Babu SG, Khatri Z, Kai W, Kim YA, Endo M, et al. Dry synthesis of easily tunable nano ruthenium supported on graphene: Novel nanocatalysts for aerial oxidation of alcohols and transfer hydrogenation of ketones. The Journal of Physical Chemistry C. 2013;**117**:23582-23596. DOI: 10.1021/jp402978q

**65**

*Preparation, Characterization, and Applications of Electrospun Carbon Nanofibers and Its…*

ja053038q

anie.200601301

10.1021/ac035143t

bios.2005.04.009

am100618h

10.1021/am9001474

10.1016/j.apcata.2008.10.016

supported nickel catalysts. Journal of the American Chemical Society. 2005;**127**:13573-13582. DOI: 10.1021/

[22] Cao L, Scheiba F, Roth C,

Chemie International Edition. 2006;**45**:5315-5319. DOI: 10.1002/

[23] Hrapovic S, Liu Y, Male KB, Luong JH. Electrochemical biosensing platforms using platinum nanoparticles and carbon nanotubes. Analytical Chemistry. 2004;**76**:1083-1088. DOI:

[24] Yang M, Yang Y, Liu Y, Shen G, Yu R. Platinum nanoparticles-doped sol–gel/carbon nanotubes composite electrochemical sensors and biosensors.

[25] Zhang Z, Shao C, Li X, Wang C,

[26] Chuangchote S, Jitputti J, Sagawa T, Yoshikawa S. Photocatalytic activity for hydrogen evolution of electrospun TiO2 nanofibers. ACS Applied Materials and Interfaces. 2009;**1**:1140-1143. DOI:

[27] Kim H, Choi Y, Kanuka N, Kinoshita H, Nishiyama T, Usami T. Preparation of Pt-loaded TiO2 nanofibers by electrospinning and their application for WGS reactions. Applied Catalysis A: General. 2009;**352**:265-270. DOI:

Biosensors and Bioelectronics. 2006;**21**:1125-1131. DOI: 10.1016/j.

Zhang M, Liu Y. Electrospun nanofibers of p-type NiO/n-type ZnO heterojunctions with enhanced

photocatalytic activity. ACS Applied Materials and Interfaces. 2010;**2**:2915-2923. DOI: 10.1021/

Schweiger F, Cremers C, Stimming U, et al. Novel nanocomposite Pt/RuO2 × H2O/carbon nanotube catalysts for direct methanol fuel cells. Angewandte

*DOI: http://dx.doi.org/10.5772/intechopen.88317*

[15] Gopiraman M, Babu SG, Khatri Z, Kai W, Kim YA, Endo M, et al. An efficient, reusable copper-oxide/carbonnanotube catalyst for N-arylation of imidazole. Carbon. 2013;**62**:135-148. DOI: 10.1016/j.carbon.2013.06.005

[16] Gopiraman M, Babu SG, Karvembu R, Kim IS. Nanostructured RuO2 on MWCNTs: Efficient catalyst for transfer hydrogenation of carbonyl compounds and aerial oxidation of alcohols. Applied Catalysis A: General. 2014;**484**:84-96. DOI: 10.1016/j.apcata.2014.06.032

[17] Gopiraman M, Bang H, Babu SG, Wei K, Karvembu R, Kim IS. Catalytic N-oxidation of tertiary amines on RuO2 NPs anchored graphene nanoplatelets. Catalytic Science and Technology. 2014;**4**:2099-2106. DOI: 10.1039/

[18] Gopiraman M, Karvembu R, Kim IS. Highly active, selective, and reusable RuO2/SWCNT catalyst for Heck olefination of aryl halides. ACS Catalysis. 2014;**4**:2118-2129. DOI:

[19] Gopiraman M, Babu SG, Khatri Z, Kai W, Kim YA, Endo M, et al. Facile and homogeneous decoration of RuO2 nanorods on graphene nanoplatelets for transfer hydrogenation of carbonyl compounds. Catalysis Science and Technology. 2013;**3**:1485-1489. DOI:

[20] Saravanamoorthy S, Chung IM, Ramkumar V, Ramaganth B, Gopiraman M. Highly active and reducing agentfree preparation of cost-effective NiObased carbon nanocomposite and its application in reduction reactions under mild conditions. Journal of Industrial and Engineering Chemistry. 2018;**60**:91- 101. DOI: 10.1016/j.jiec.2017.10.006

[21] van der Lee MK, van Dillen J, Bitter JH, de Jong KP. Deposition precipitation for the preparation of carbon nanofiber

C3CY00963G

10.1021/cs500460m

10.1039/C3CY20735H

*Preparation, Characterization, and Applications of Electrospun Carbon Nanofibers and Its… DOI: http://dx.doi.org/10.5772/intechopen.88317*

[15] Gopiraman M, Babu SG, Khatri Z, Kai W, Kim YA, Endo M, et al. An efficient, reusable copper-oxide/carbonnanotube catalyst for N-arylation of imidazole. Carbon. 2013;**62**:135-148. DOI: 10.1016/j.carbon.2013.06.005

[16] Gopiraman M, Babu SG, Karvembu R, Kim IS. Nanostructured RuO2 on MWCNTs: Efficient catalyst for transfer hydrogenation of carbonyl compounds and aerial oxidation of alcohols. Applied Catalysis A: General. 2014;**484**:84-96. DOI: 10.1016/j.apcata.2014.06.032

[17] Gopiraman M, Bang H, Babu SG, Wei K, Karvembu R, Kim IS. Catalytic N-oxidation of tertiary amines on RuO2 NPs anchored graphene nanoplatelets. Catalytic Science and Technology. 2014;**4**:2099-2106. DOI: 10.1039/ C3CY00963G

[18] Gopiraman M, Karvembu R, Kim IS. Highly active, selective, and reusable RuO2/SWCNT catalyst for Heck olefination of aryl halides. ACS Catalysis. 2014;**4**:2118-2129. DOI: 10.1021/cs500460m

[19] Gopiraman M, Babu SG, Khatri Z, Kai W, Kim YA, Endo M, et al. Facile and homogeneous decoration of RuO2 nanorods on graphene nanoplatelets for transfer hydrogenation of carbonyl compounds. Catalysis Science and Technology. 2013;**3**:1485-1489. DOI: 10.1039/C3CY20735H

[20] Saravanamoorthy S, Chung IM, Ramkumar V, Ramaganth B, Gopiraman M. Highly active and reducing agentfree preparation of cost-effective NiObased carbon nanocomposite and its application in reduction reactions under mild conditions. Journal of Industrial and Engineering Chemistry. 2018;**60**:91- 101. DOI: 10.1016/j.jiec.2017.10.006

[21] van der Lee MK, van Dillen J, Bitter JH, de Jong KP. Deposition precipitation for the preparation of carbon nanofiber

supported nickel catalysts. Journal of the American Chemical Society. 2005;**127**:13573-13582. DOI: 10.1021/ ja053038q

[22] Cao L, Scheiba F, Roth C, Schweiger F, Cremers C, Stimming U, et al. Novel nanocomposite Pt/RuO2 × H2O/carbon nanotube catalysts for direct methanol fuel cells. Angewandte Chemie International Edition. 2006;**45**:5315-5319. DOI: 10.1002/ anie.200601301

[23] Hrapovic S, Liu Y, Male KB, Luong JH. Electrochemical biosensing platforms using platinum nanoparticles and carbon nanotubes. Analytical Chemistry. 2004;**76**:1083-1088. DOI: 10.1021/ac035143t

[24] Yang M, Yang Y, Liu Y, Shen G, Yu R. Platinum nanoparticles-doped sol–gel/carbon nanotubes composite electrochemical sensors and biosensors. Biosensors and Bioelectronics. 2006;**21**:1125-1131. DOI: 10.1016/j. bios.2005.04.009

[25] Zhang Z, Shao C, Li X, Wang C, Zhang M, Liu Y. Electrospun nanofibers of p-type NiO/n-type ZnO heterojunctions with enhanced photocatalytic activity. ACS Applied Materials and Interfaces. 2010;**2**:2915-2923. DOI: 10.1021/ am100618h

[26] Chuangchote S, Jitputti J, Sagawa T, Yoshikawa S. Photocatalytic activity for hydrogen evolution of electrospun TiO2 nanofibers. ACS Applied Materials and Interfaces. 2009;**1**:1140-1143. DOI: 10.1021/am9001474

[27] Kim H, Choi Y, Kanuka N, Kinoshita H, Nishiyama T, Usami T. Preparation of Pt-loaded TiO2 nanofibers by electrospinning and their application for WGS reactions. Applied Catalysis A: General. 2009;**352**:265-270. DOI: 10.1016/j.apcata.2008.10.016

**64**

*Electrospinning and Electrospraying - Techniques and Applications*

[9] Selvamani A, Babu CM, Ramkumar V, Sundaravel B. Reduced graphene oxide decorated Au nanoparticles as an efficient electrode for the determination of hydroquinone. Nano Progress.

[10] Day TM, Unwin PR, Macpherson

electrodeposition of metal nanoparticles

[12] Yuan G, Gopiraman M, Cha HJ, Soo HD, Chung IM, Kim IS. Interconnected ruthenium dioxide nanoparticles anchored on graphite oxide: Highly efficient candidate for solvent-free oxidative synthesis of imines. Journal of Industrial and Engineering Chemistry. 2017;**46**:279-288. DOI: 10.1016/j.

[13] Gopiraman M, Deng D, Babu SG,

[14] Gopiraman M, Babu SG, Khatri Z, Kai W, Kim YA, Endo M, et al. Dry synthesis of easily tunable nano ruthenium supported on graphene: Novel nanocatalysts for aerial oxidation of alcohols and transfer hydrogenation of ketones. The Journal of Physical Chemistry C. 2013;**117**:23582-23596.

Hayashi T, Karvembu R, Kim IS. Sustainable and versatile CuO/ GNS nanocatalyst for highly efficient base free coupling reactions. ACS Sustainable Chemical Engineering. 2015;**3**:2478-2488. DOI: 10.1021/

acssuschemeng.5b00542

DOI: 10.1021/jp402978q

JV. Factors controlling the

DOI: 10.1021/nl061974d

[11] Lin Z, Ji L, Zhang X. Electrodeposition of platinum nanoparticles onto carbon nanofibers

matlet.2009.07.005

jiec.2016.10.040

for electrocatalytic oxidation of methanol. Materials Letters. 2009;**63**:2115-2118. DOI: 10.1016/j.

on pristine single walled carbon nanotubes. Nano Letters. 2007;**7**:51-57.

2019;**1**:9-14

[1] Burda C, Chen XB, Narayanan R, El-Sayed MA. Chemistry and properties of nanocrystals of different shapes. Chemical Reviews. 2005;**105**:1025-1102.

[2] De Jong KP, Geus JW. Carbon nanofibers: Catalytic synthesis and applications. Catalysis Reviews. 2000;**42**:481-510. DOI: 10.1081/

[3] Vamvakaki V, Tsagaraki K,

Chaniotakis N. Carbon nanofiber-based glucose biosensor. Analytical Chemistry. 2006;**78**:5538-5542. DOI: 10.1021/

[4] Kim C, Yang KS, Kojima M, Yoshida K, Kim YJ, Kim YA, et al. Fabrication of electrospinning‐derived carbon nanofiber webs for the anode material of lithium‐ion secondary batteries. Advanced Functional Materials. 2006;**16**:2393-2397. DOI: 10.1002/

[5] Huang CB, Chen SL, Reneker DH, Lai CL, Hou HQ. High‐strength mats from electrospun poly(p‐phenylene biphenyltetracarboximide) nanofibers. Advanced Materials. 2006;**18**:668-671.

DOI: 10.1002/adma.200501806

[7] Wang Y, Santiago-Aviles JJ. Conductivity measurement of electrospun PAN-based carbon

Letters. 2002;**21**:1055-1057

10.1021/ja055530f

[6] Donnet JB, Bansal RC. Carbon Fibers. New York: Marcel Dekker; 1990

nanofiber. Journal of Materials Science

[8] Yoon B, Wai CM. Microemulsiontemplated synthesis of carbon nanotube-supported Pd and Rh

nanoparticles for catalytic applications. Journal of the American Chemical Society. 2005;**127**(49):17174-17175. DOI:

DOI: 10.1021/cr030063a

CR-100101954

**References**

ac060551t

adfm.200500911

[28] Wang ZG, Wan LS, Liu ZM, Huang XJ, Xu ZK. Enzyme immobilization on electrospun polymer nanofibers: An overview. Journal of Molecular Catalysis B: Enzymatic. 2009;**56**:189-195. DOI: 10.1016/j.molcatb.2008.05.005

[29] Wan LS, Ke BB, Wu J, Xu ZK. Catalase immobilization on electrospun nanofibers: Effects of porphyrin pendants and carbon nanotubes. The Journal of Physical Chemistry C. 2007;**111**:14091-14097. DOI: 10.1021/ jp070983n

[30] Barakat NA, El-Newehy M, Al-Deyab SS, Kim HY. Cobalt/copperdecorated carbon nanofibers as novel non-precious electrocatalyst for methanol electrooxidation. Nanoscale Research Letters. 2014;**9**:2. DOI: 10.1186/1556-276X-9-2

[31] Ye XR, Lin Y, Wang C, Engelhard MH, Wang Y, Wai CM. Supercritical fluid synthesis and characterization of catalytic metal nanoparticles on carbon nanotubes. Journal of Materials Chemistry. 2004;**14**(5):908-913. DOI: 10.1039/B308124A

[32] Yang W, Yang S, Guo J, Sun G, Xin Q. Comparison of CNF and XC-72 carbon supported palladium electrocatalysts for magnesium air fuel cell. Carbon. 2007;**45**:397-401. DOI: 10.1016/j.carbon.2006.09.003

[33] Guo DJ, Li HL. Electrochemical synthesis of Pd nanoparticles on functional MWNT surfaces. Electrochemistry Communications. 2004;**6**:999-1003. DOI: 10.1016/j. elecom.2004.07.014

[34] Li D, Xia Y. Electrospinning of nanofibers: Reinventing the wheel? Advanced Materials. 2004;**16**:1151-1170. DOI: 10.1002/adma.200400719

[35] Park JY, Lee IH, Bea GN. Optimization of the electrospinning conditions for preparation of

nanofibers from polyvinylacetate (PVAc) in ethanol solvent. Journal of Industrial and Engineering Chemistry. 2008;**14**:707-713. DOI: 10.1016/j. jiec.2008.03.006

[36] Inagaki M, Yang Y, Kang F. Carbon nanofibers prepared via electrospinning. Advanced Materials. 2012;**24**:2547-2566. DOI: 10.1002/adma.201104940

[37] Kim C, Yang KS. Electrochemical properties of carbon nanofiber web as an electrode for supercapacitor prepared by electrospinning. Applied Physics Letters. 2003;**83**:1216-1218. DOI: 10.1063/1.1599963

[38] Kuzmenko V, Naboka O, Gatenholm P, Enoksson P. Ammonium chloride promoted synthesis of carbon nanofibers from electrospun cellulose acetate. Carbon. 2014;**67**:694-703. DOI: 10.1016/j.carbon.2013.10.061

[39] Kim C, Jeong YI, Ngoc BTN, Yang KS, Kojima M, Kim YA, et al. Synthesis and characterization of porous carbon nanofibers with hollow cores through the thermal treatment of electrospun copolymeric nanofiber webs. Small. 2007;**3**:91-95. DOI: 10.1002/ smll.200600243

[40] Brandrup J, Immergut EH, Grulke EA, Abe A, Bloch DR, editors. Polymer Handbook. Vol. 89. New York: Wiley; 1999

[41] Wei K, Kim KO, Song KH, Kang CY, Lee JS, Gopiraman M, et al. Nitrogenand oxygen-containing porous ultrafine carbon nanofiber: A highly flexible electrode material for supercapacitor. Journal of Materials Science and Technology. 2017;**33**:424-431. DOI: 10.1016/j.jmst.2016.03.014

[42] Chang WM, Wang CC, Chen CY. Fabrication of ultra-thin carbon nanofibers by centrifugedelectrospinning for application in highrate supercapacitors. Electrochimica

**67**

ceramint.2014.10.031

*Preparation, Characterization, and Applications of Electrospun Carbon Nanofibers and Its…*

of methanol on Pt nanostructures supported on electrospun nanofibers of anatase. The Journal of Physical Chemistry C. 2008;**112**:9970-9975. DOI:

[50] Sonogashira K. Development of Pd– Cu catalyzed cross-coupling of terminal acetylenes with sp2-carbon halides. Journal of Organometallic Chemistry.

2002;**653**:46-49. DOI: 10.1016/ S0022-328X(02)01158-0

[51] Gopiraman M, Deng D,

Saravanamoorthy S, Chung IM, Kim IS. Gold, silver and nickel nanoparticle anchored cellulose nanofiber composites as highly active catalysts for the rapid and selective reduction of nitrophenols in water. RSC Advances. 2018;**8**:3014- 3023. DOI: 10.1039/C7RA10489H

[52] Chang YC, Chen DH. Catalytic reduction of 4-nitrophenol by magnetically recoverable Au nanocatalyst. Journal of Hazardous Materials. 2009;**165**:664-669. DOI: 10.1016/j.jhazmat.2008.10.034

[53] Gopiraman M, Saravanamoorthy S, Chung IM. Highly active humanhair-supported noble metal (Ag or Ru) nanocomposites for rapid and selective reduction of p-nitrophenol to p-aminophenol. Research on Chemical Intermediates. 2017;**43**:5601-5614. DOI:

[54] Gopiraman M, Deng D, Kim BS, Chung IM, Kim IS. Three-dimensional cheese-like carbon nanoarchitecture with tremendous surface area and pore construction derived from corn as superior electrode materials for supercapacitors. Applied Surface Science. 2017;**409**:52-59. DOI: 10.1016/j.

10.1007/s11164-017-2950-3

apsusc.2017.02.209

10.1021/jp803763q

*DOI: http://dx.doi.org/10.5772/intechopen.88317*

Acta. 2019;**296**:268-275. DOI: 10.1016/j.

[43] Endo M, Kim YA, Ezaka M, Osada K, Yanagisawa T, Hayashi T, et al. Selective and efficient impregnation of metal nanoparticles on cup-stackedtype carbon nanofibers. Nano Letters. 2003;**3**:723-726. DOI: 10.1021/nl034136h

[44] Atchison JS, Zeiger M, Tolosa A, Funke LM, Jäckel N, Presser V. Electrospinning of ultrafine metal oxide/carbon and metal carbide/carbon nanocomposite fibers. RSC Advances. 2015;**5**:35683-35692. DOI: 10.1039/

[45] Chen L, Hong S, Zhou X, Zhou Z, Hou H. Novel Pd-carrying composite carbon nanofibers based on polyacrylonitrile as a catalyst for Sonogashira coupling reaction. Catalysis Communications. 2008;**9**:2221-2225. DOI: 10.1016/j.catcom.2008.05.002

[46] Zhang P, Shao C, Zhang Z, Zhang M, Mu J, Guo Z, et al. In situ assembly of well-dispersed Ag nanoparticles (AgNPs) on electrospun carbon nanofibers (CNFs) for catalytic

reduction of 4-nitrophenol. Nanoscale.

[48] Ghouri ZK, Barakat NA, Obaid M, Lee JH, Kim HY. Co/CeO2-decorated carbon nanofibers as effective non-precious electro-catalyst for fuel cells application in alkaline medium. Ceramics International. 2015;**41**:2271-2278. DOI: 10.1016/j.

[49] Formo E, Peng Z, Lee E, Lu X, Yang H, Xia Y. Direct oxidation

2011;**3**:357-3363. DOI: 10.1039/

[47] Yu B, Liu Y, Jiang G, Liu D, Yu W, Chen H, et al. Preparation of electrospun Ag/g-C3N4 loaded composite carbon nanofibers for catalytic applications. Materials Research Express. 2017;**4**:015603

C1NR10405E

electacta.2018.08.048

C5RA05409E

*Preparation, Characterization, and Applications of Electrospun Carbon Nanofibers and Its… DOI: http://dx.doi.org/10.5772/intechopen.88317*

Acta. 2019;**296**:268-275. DOI: 10.1016/j. electacta.2018.08.048

*Electrospinning and Electrospraying - Techniques and Applications*

nanofibers from polyvinylacetate (PVAc) in ethanol solvent. Journal of Industrial and Engineering Chemistry. 2008;**14**:707-713. DOI: 10.1016/j.

[36] Inagaki M, Yang Y, Kang F. Carbon nanofibers prepared via electrospinning. Advanced Materials. 2012;**24**:2547-2566.

[37] Kim C, Yang KS. Electrochemical properties of carbon nanofiber web as an electrode for supercapacitor prepared by electrospinning. Applied Physics Letters. 2003;**83**:1216-1218. DOI:

[38] Kuzmenko V, Naboka O, Gatenholm P, Enoksson P. Ammonium chloride promoted synthesis of carbon

nanofibers from electrospun cellulose acetate. Carbon. 2014;**67**:694-703. DOI:

[39] Kim C, Jeong YI, Ngoc BTN, Yang KS, Kojima M, Kim YA, et al. Synthesis and characterization of porous carbon nanofibers with hollow cores through the thermal treatment of electrospun

[40] Brandrup J, Immergut EH, Grulke EA, Abe A, Bloch DR, editors. Polymer Handbook. Vol. 89. New York: Wiley;

[41] Wei K, Kim KO, Song KH, Kang CY, Lee JS, Gopiraman M, et al. Nitrogenand oxygen-containing porous ultrafine carbon nanofiber: A highly flexible electrode material for supercapacitor. Journal of Materials Science and Technology. 2017;**33**:424-431. DOI:

[42] Chang WM, Wang CC, Chen CY. Fabrication of ultra-thin carbon nanofibers by centrifuged-

electrospinning for application in highrate supercapacitors. Electrochimica

10.1016/j.carbon.2013.10.061

copolymeric nanofiber webs. Small. 2007;**3**:91-95. DOI: 10.1002/

10.1016/j.jmst.2016.03.014

smll.200600243

1999

DOI: 10.1002/adma.201104940

jiec.2008.03.006

10.1063/1.1599963

[28] Wang ZG, Wan LS, Liu ZM, Huang XJ, Xu ZK. Enzyme immobilization on electrospun polymer nanofibers: An overview. Journal of Molecular Catalysis B: Enzymatic. 2009;**56**:189-195. DOI: 10.1016/j.molcatb.2008.05.005

[29] Wan LS, Ke BB, Wu J, Xu ZK. Catalase immobilization on electrospun

nanofibers: Effects of porphyrin pendants and carbon nanotubes. The Journal of Physical Chemistry C. 2007;**111**:14091-14097. DOI: 10.1021/

[30] Barakat NA, El-Newehy M, Al-Deyab SS, Kim HY. Cobalt/copperdecorated carbon nanofibers as novel non-precious electrocatalyst for methanol electrooxidation. Nanoscale Research Letters. 2014;**9**:2. DOI:

[31] Ye XR, Lin Y, Wang C, Engelhard MH, Wang Y, Wai CM. Supercritical fluid synthesis and characterization of catalytic metal nanoparticles on carbon nanotubes. Journal of Materials Chemistry. 2004;**14**(5):908-913. DOI:

[32] Yang W, Yang S, Guo J, Sun G, Xin Q. Comparison of CNF and XC-72 carbon supported palladium electrocatalysts for magnesium air fuel cell. Carbon. 2007;**45**:397-401. DOI: 10.1016/j.carbon.2006.09.003

[33] Guo DJ, Li HL. Electrochemical synthesis of Pd nanoparticles on functional MWNT surfaces. Electrochemistry Communications. 2004;**6**:999-1003. DOI: 10.1016/j.

[34] Li D, Xia Y. Electrospinning of nanofibers: Reinventing the wheel? Advanced Materials. 2004;**16**:1151-1170.

Optimization of the electrospinning conditions for preparation of

DOI: 10.1002/adma.200400719

[35] Park JY, Lee IH, Bea GN.

10.1186/1556-276X-9-2

10.1039/B308124A

elecom.2004.07.014

jp070983n

**66**

[43] Endo M, Kim YA, Ezaka M, Osada K, Yanagisawa T, Hayashi T, et al. Selective and efficient impregnation of metal nanoparticles on cup-stackedtype carbon nanofibers. Nano Letters. 2003;**3**:723-726. DOI: 10.1021/nl034136h

[44] Atchison JS, Zeiger M, Tolosa A, Funke LM, Jäckel N, Presser V. Electrospinning of ultrafine metal oxide/carbon and metal carbide/carbon nanocomposite fibers. RSC Advances. 2015;**5**:35683-35692. DOI: 10.1039/ C5RA05409E

[45] Chen L, Hong S, Zhou X, Zhou Z, Hou H. Novel Pd-carrying composite carbon nanofibers based on polyacrylonitrile as a catalyst for Sonogashira coupling reaction. Catalysis Communications. 2008;**9**:2221-2225. DOI: 10.1016/j.catcom.2008.05.002

[46] Zhang P, Shao C, Zhang Z, Zhang M, Mu J, Guo Z, et al. In situ assembly of well-dispersed Ag nanoparticles (AgNPs) on electrospun carbon nanofibers (CNFs) for catalytic reduction of 4-nitrophenol. Nanoscale. 2011;**3**:357-3363. DOI: 10.1039/ C1NR10405E

[47] Yu B, Liu Y, Jiang G, Liu D, Yu W, Chen H, et al. Preparation of electrospun Ag/g-C3N4 loaded composite carbon nanofibers for catalytic applications. Materials Research Express. 2017;**4**:015603

[48] Ghouri ZK, Barakat NA, Obaid M, Lee JH, Kim HY. Co/CeO2-decorated carbon nanofibers as effective non-precious electro-catalyst for fuel cells application in alkaline medium. Ceramics International. 2015;**41**:2271-2278. DOI: 10.1016/j. ceramint.2014.10.031

[49] Formo E, Peng Z, Lee E, Lu X, Yang H, Xia Y. Direct oxidation

of methanol on Pt nanostructures supported on electrospun nanofibers of anatase. The Journal of Physical Chemistry C. 2008;**112**:9970-9975. DOI: 10.1021/jp803763q

[50] Sonogashira K. Development of Pd– Cu catalyzed cross-coupling of terminal acetylenes with sp2-carbon halides. Journal of Organometallic Chemistry. 2002;**653**:46-49. DOI: 10.1016/ S0022-328X(02)01158-0

[51] Gopiraman M, Deng D, Saravanamoorthy S, Chung IM, Kim IS. Gold, silver and nickel nanoparticle anchored cellulose nanofiber composites as highly active catalysts for the rapid and selective reduction of nitrophenols in water. RSC Advances. 2018;**8**:3014- 3023. DOI: 10.1039/C7RA10489H

[52] Chang YC, Chen DH. Catalytic reduction of 4-nitrophenol by magnetically recoverable Au nanocatalyst. Journal of Hazardous Materials. 2009;**165**:664-669. DOI: 10.1016/j.jhazmat.2008.10.034

[53] Gopiraman M, Saravanamoorthy S, Chung IM. Highly active humanhair-supported noble metal (Ag or Ru) nanocomposites for rapid and selective reduction of p-nitrophenol to p-aminophenol. Research on Chemical Intermediates. 2017;**43**:5601-5614. DOI: 10.1007/s11164-017-2950-3

[54] Gopiraman M, Deng D, Kim BS, Chung IM, Kim IS. Three-dimensional cheese-like carbon nanoarchitecture with tremendous surface area and pore construction derived from corn as superior electrode materials for supercapacitors. Applied Surface Science. 2017;**409**:52-59. DOI: 10.1016/j. apsusc.2017.02.209

**69**

Section 3

Electrospraying

Section 3 Electrospraying

**71**

**Chapter 4**

**Abstract**

promising results.

biological activity

**1. Introduction**

Effect of Spray-Drying and

Electrospraying as Drying

*Ijeoma Abraham, Eman Ali Elkordy, Rita Haj Ahmad,* 

The production of biopharmaceutical formulation incorporates several difficulties embracing their physical and chemical instabilities. In this study, two drying techniques, namely, spray-drying and electrospraying, were used to assess their application on lysozyme (as a model protein) without and with the use of betacyclodextrin. Samples were prepared in the ratio of 1:1 w/w (protein/ betacyclodextrin), and several characterisation methods were applied to study the percentage (%) yield, morphology of the produced partials, thermal stability and biological activity of the protein. The results show the two drying methods led to different particle morphology as spherical-like shape was produced by spray-drying, while rodlike shape was generated by electrospraying with larger particle size. Lysozyme formulations produced by electrospraying were stable just directly after preparation, but after few weeks, those formulations showed visible aggregates. The biological activity of lysozyme was preserved by both drying techniques. In conclusion, both drying methods have different effects on the protein integrity and biological activity in which spray-drying shows more

**Keywords:** lysozyme, spray-drying, electrospraying, thermal stability,

The majority of the FDA-approved protein-based medicines are delivered via conventional injection route (e.g. subcutaneous, intramuscular or intravenous). The pharmaceutical industries are faced with one of the most significant problems in protein manufacturing. One of the setbacks is the stability in the processing, manufacturing and storage of these therapeutic drugs. Solid dosage forms of therapeutic proteins could improve protein's bioavailability and stability during processing and storage. Various formulation techniques were applied utilising drying process aiming to develop a stable protein formulation (e.g. spray-drying, freeze drying, electrospraying, electrospinning, etc.). This chapter will be looking at the stability of lysozyme as a model of protein using spray-drying technique and

Techniques on Lysozyme

*Zeeshan Ahmad and Amal Ali Elkordy*

Characterisation

### **Chapter 4**

## Effect of Spray-Drying and Electrospraying as Drying Techniques on Lysozyme Characterisation

*Ijeoma Abraham, Eman Ali Elkordy, Rita Haj Ahmad, Zeeshan Ahmad and Amal Ali Elkordy*

### **Abstract**

The production of biopharmaceutical formulation incorporates several difficulties embracing their physical and chemical instabilities. In this study, two drying techniques, namely, spray-drying and electrospraying, were used to assess their application on lysozyme (as a model protein) without and with the use of betacyclodextrin. Samples were prepared in the ratio of 1:1 w/w (protein/ betacyclodextrin), and several characterisation methods were applied to study the percentage (%) yield, morphology of the produced partials, thermal stability and biological activity of the protein. The results show the two drying methods led to different particle morphology as spherical-like shape was produced by spray-drying, while rodlike shape was generated by electrospraying with larger particle size. Lysozyme formulations produced by electrospraying were stable just directly after preparation, but after few weeks, those formulations showed visible aggregates. The biological activity of lysozyme was preserved by both drying techniques. In conclusion, both drying methods have different effects on the protein integrity and biological activity in which spray-drying shows more promising results.

**Keywords:** lysozyme, spray-drying, electrospraying, thermal stability, biological activity

#### **1. Introduction**

The majority of the FDA-approved protein-based medicines are delivered via conventional injection route (e.g. subcutaneous, intramuscular or intravenous). The pharmaceutical industries are faced with one of the most significant problems in protein manufacturing. One of the setbacks is the stability in the processing, manufacturing and storage of these therapeutic drugs. Solid dosage forms of therapeutic proteins could improve protein's bioavailability and stability during processing and storage. Various formulation techniques were applied utilising drying process aiming to develop a stable protein formulation (e.g. spray-drying, freeze drying, electrospraying, electrospinning, etc.). This chapter will be looking at the stability of lysozyme as a model of protein using spray-drying technique and electrohydrodynamic atomisation (EHDA) also known as electrospray. Very few publications have looked at the stability of lysozyme using EHDA technique. This challenge has necessitated the contribution towards this area.

#### **1.1 Proteins**

Proteins are macromolecules which require their native structure to be biologically active, and their conformation is very important in the development of protein drugs. They may denature with structural changes under stress, and there will be a loss of activities in the molecules. Examples of stresses are heat, elevated temperature, pressure, surface adsorption and pH [1]. Proteins undergo physical and chemical degradation; examples of physical degradation include aggregation, precipitation and unfolding as updated in Hui et al. [2] which involves the transition of protein from its native state to an unfolded state and will follow a significant loss in the function of a protein which generally will cause an unstable solution during the processing, manufacturing and storage.

#### **1.2 Structure of proteins**

Proteins consist of chains or small units of amino acid also known as amino acid polymers or building blocks [3] which contain the backbone or main chain of repeated units with attachments of variable side chains and are linked by peptide bonds. Each protein has a unique sequence of the side chains which determines the characteristics of the individual chain. There is a free carboxyl terminal at the end and a free amino terminal at the other end of every protein except for few cyclic polypeptides. The amino acid sequence is given in order of N-terminal to the C-terminal [4].

They are macromolecules heterogeneous in their native environment and are in most cases unstable. The ordering sequences in amino acids are referred to as the primary structure of protein and the secondary structure (α helix and β sheet); these are three-dimensional elements which all have an orientation of the protein backbone; tertiary structure is formed from secondary structural elements [5]; and quaternary structure comprises of several subunits with tertiary structures [6]. The configuration is determined by the native form followed by the assignment of α helix and β sheet which produces secondary conformation as these molecules are all linked by hydrogen bond [7].

This stability of the protein structure should include the three-dimensional state, the folded and the tertiary state which are all required for the biological activity. Although conformational stability is not enough rather, the protein must be able to find the folding pathway or its state within a short time from a denatured, unfolded conformation [8]. Folding maximises exposure of polar groups to the solvent and minimises exposure of non-polar groups. Protein unfolding is the transition from a native form to a denatured state [9]. When molecules are in aqueous solution, there is an equilibrium between folded which is the native state conformation and unfolded known as denatured. Native conformation stability is based on the relationship thermodynamically between ΔS and ΔH and the extent of ΔG-Gibbs free energy of the system. When the magnitude of ΔG is negative, it shows that there is a high stability of the native conformation than the denatured state which means that the greater the stability, the more negative is the ΔG. During protein unfolding, the main critical bonds required for protein stabilization are broken. Unfolding of proteins can take place at high temperatures, where the entropy is the main factor and the conformational entropy overpowers stabilizing forces. Hence, protein unfolding takes place. DSC takes measurement of ΔH of unfolding as a result of heat denaturation [10, 11].

**73**

point of 10.7.

*Effect of Spray-Drying and Electrospraying as Drying Techniques on Lysozyme Characterisation*

Stability of protein is the achievement of a balance between stabilising and destabilising forces. The stabilising forces are caused by protein-solvent and intraprotein interaction, while the other is caused by substantial increase in entropy of

One of the major challenges with the biopharmaceuticals is achieving protein

Conformational stability describes the ability of the protein to maintain its native structure and be properly folded. Chemical stability is the stability among amino acid, covalent bond and different protein domains, while colloidal stability is the ability of the native structure of protein in a solution to avoid precipitation, aggregation and phase separation. However, it is necessary to maintain all types of stability during all the stages of development, processing and manufacturing. The instability of protein necessitates the production in solid forms as solid proteins can be crystallised and dried [13] and its administration as a drug injection rather than through oral means like other drugs. Therefore, excipients also known as stabilisers are introduced to preserve the state and folding reversibility of proteins and reduce aggregation [14]. In effect to tackle protein degradation, necessary precautions and measures are taken to select the appropriate formulations for any

Proteins produced in different forms, like liquid formulations for medicines, are injectable due to the ease of preparation and are the most preferred, in manufacturing as well as the end users [15]. Unfortunately, it is not convenient due to the susceptibility of these proteins to the risk factors. This has instigated the consideration of the use of excipients as earlier mentioned in a dry solid state as important. Glass-forming agents such as saccharides, polyols and organic acids have been studied extensively over the years to stabilise spray-dried proteins in the solid state [16, 17]; these excipients stabilise the macromolecules by two primary mechanisms. Usually, the glass-forming ability of these excipients preserves the structure of

Lysozyme (1,4-β-N-acetylmuramidase) is the model of protein used in this study because lysozyme is one of the most potent proteins containing about 129 amino acids and has a high ionic strength. pH and the enzymes depend highly on their tertiary structure for maintaining their biological activity [20]. Lysozyme is folded into globular compact structure with a long cleft in the surface of the protein. The binding of the bacterial carbohydrate chain and the cleaving take place in the active site known as the cleft [21]; it has a molecular weight of 14.3 kDa and an isoelectric

Lysozyme can be protected against bacteria through its activity as an enzyme as the role of an enzyme is to speed up the rate of chemical reaction in the body. Usually, polysaccharides are found in the cell walls of the affected bacteria which

*DOI: http://dx.doi.org/10.5772/intechopen.86237*

There are three (3) types of stability:

excipients as well as the right technique for optimisation.

proteins by trapping it in a rigid amorphous glass matrix [18, 19].

**1.4 Lysozyme as a protein model**

1.Conformational stability

2.Chemical stability

3.Colloidal stability

**1.3 Stability of proteins**

unfolding [12].

stability.

*Effect of Spray-Drying and Electrospraying as Drying Techniques on Lysozyme Characterisation DOI: http://dx.doi.org/10.5772/intechopen.86237*

#### **1.3 Stability of proteins**

*Electrospinning and Electrospraying - Techniques and Applications*

during the processing, manufacturing and storage.

**1.2 Structure of proteins**

linked by hydrogen bond [7].

C-terminal [4].

**1.1 Proteins**

challenge has necessitated the contribution towards this area.

electrohydrodynamic atomisation (EHDA) also known as electrospray. Very few publications have looked at the stability of lysozyme using EHDA technique. This

Proteins are macromolecules which require their native structure to be biologically active, and their conformation is very important in the development of protein drugs. They may denature with structural changes under stress, and there will be a loss of activities in the molecules. Examples of stresses are heat, elevated temperature, pressure, surface adsorption and pH [1]. Proteins undergo physical and chemical degradation; examples of physical degradation include aggregation, precipitation and unfolding as updated in Hui et al. [2] which involves the transition of protein from its native state to an unfolded state and will follow a significant loss in the function of a protein which generally will cause an unstable solution

Proteins consist of chains or small units of amino acid also known as amino acid polymers or building blocks [3] which contain the backbone or main chain of repeated units with attachments of variable side chains and are linked by peptide bonds. Each protein has a unique sequence of the side chains which determines the characteristics of the individual chain. There is a free carboxyl terminal at the end and a free amino terminal at the other end of every protein except for few cyclic polypeptides. The amino acid sequence is given in order of N-terminal to the

They are macromolecules heterogeneous in their native environment and are in most cases unstable. The ordering sequences in amino acids are referred to as the primary structure of protein and the secondary structure (α helix and β sheet); these are three-dimensional elements which all have an orientation of the protein backbone; tertiary structure is formed from secondary structural elements [5]; and quaternary structure comprises of several subunits with tertiary structures [6]. The configuration is determined by the native form followed by the assignment of α helix and β sheet which produces secondary conformation as these molecules are all

This stability of the protein structure should include the three-dimensional state,

the folded and the tertiary state which are all required for the biological activity. Although conformational stability is not enough rather, the protein must be able to find the folding pathway or its state within a short time from a denatured, unfolded conformation [8]. Folding maximises exposure of polar groups to the solvent and minimises exposure of non-polar groups. Protein unfolding is the transition from a native form to a denatured state [9]. When molecules are in aqueous solution, there is an equilibrium between folded which is the native state conformation and unfolded known as denatured. Native conformation stability is based on the relationship thermodynamically between ΔS and ΔH and the extent of ΔG-Gibbs free energy of the system. When the magnitude of ΔG is negative, it shows that there is a high stability of the native conformation than the denatured state which means that the greater the stability, the more negative is the ΔG. During protein unfolding, the main critical bonds required for protein stabilization are broken. Unfolding of proteins can take place at high temperatures, where the entropy is the main factor and the conformational entropy overpowers stabilizing forces. Hence, protein unfolding takes place. DSC takes measurement of ΔH of unfolding as a result of heat denaturation [10, 11].

**72**

Stability of protein is the achievement of a balance between stabilising and destabilising forces. The stabilising forces are caused by protein-solvent and intraprotein interaction, while the other is caused by substantial increase in entropy of unfolding [12].

One of the major challenges with the biopharmaceuticals is achieving protein stability.

There are three (3) types of stability:


Conformational stability describes the ability of the protein to maintain its native structure and be properly folded. Chemical stability is the stability among amino acid, covalent bond and different protein domains, while colloidal stability is the ability of the native structure of protein in a solution to avoid precipitation, aggregation and phase separation. However, it is necessary to maintain all types of stability during all the stages of development, processing and manufacturing.

The instability of protein necessitates the production in solid forms as solid proteins can be crystallised and dried [13] and its administration as a drug injection rather than through oral means like other drugs. Therefore, excipients also known as stabilisers are introduced to preserve the state and folding reversibility of proteins and reduce aggregation [14]. In effect to tackle protein degradation, necessary precautions and measures are taken to select the appropriate formulations for any excipients as well as the right technique for optimisation.

Proteins produced in different forms, like liquid formulations for medicines, are injectable due to the ease of preparation and are the most preferred, in manufacturing as well as the end users [15]. Unfortunately, it is not convenient due to the susceptibility of these proteins to the risk factors. This has instigated the consideration of the use of excipients as earlier mentioned in a dry solid state as important. Glass-forming agents such as saccharides, polyols and organic acids have been studied extensively over the years to stabilise spray-dried proteins in the solid state [16, 17]; these excipients stabilise the macromolecules by two primary mechanisms. Usually, the glass-forming ability of these excipients preserves the structure of proteins by trapping it in a rigid amorphous glass matrix [18, 19].

#### **1.4 Lysozyme as a protein model**

Lysozyme (1,4-β-N-acetylmuramidase) is the model of protein used in this study because lysozyme is one of the most potent proteins containing about 129 amino acids and has a high ionic strength. pH and the enzymes depend highly on their tertiary structure for maintaining their biological activity [20]. Lysozyme is folded into globular compact structure with a long cleft in the surface of the protein. The binding of the bacterial carbohydrate chain and the cleaving take place in the active site known as the cleft [21]; it has a molecular weight of 14.3 kDa and an isoelectric point of 10.7.

Lysozyme can be protected against bacteria through its activity as an enzyme as the role of an enzyme is to speed up the rate of chemical reaction in the body. Usually, polysaccharides are found in the cell walls of the affected bacteria which contain amine groups (NH2) with sugar and side chains of sugar. Addition of water molecules to the sugar linkage causes lysozyme to degrade the polysaccharide, thereby causing it to break open. Its activity is a function of the ionic strength and pH. It is active between a pH of 6.0 and pH 9.0. Maximum activity is observed at a pH of 6.2 and ionic strength 0.02–0.100 M compared to 0.01–0.06 M at pH 9.2.

#### **1.5 Drying techniques**

#### *1.5.1 Electrohydrodynamic atomisation*

EHDA also known as electrospray is a drying technique used in the production of dry powder with the help of charges. It was first observed and recorded by Williams Gilbert in 1600 [22]. It is a process where a liquid imposes through a nozzle (which is connected to a voltage supply) at a certain flow rate, subjecting to high potential electric field. As a result, the meniscus is elongated to form a jet that breaks up into droplet under electrical force influence. Particles can then be collected at a collecting platform that is located ~20 cm under the spraying nozzle (**Figure 1**). Various spraying modes can be obtained depending on the strength of the electric stress and on the kinetic energy of the liquid leaving the nozzle for nanoparticle production. It is a well-practised technique for generating very fine droplets with monodispersed size from the liquid under the influence of electric forces [23]. It can achieve controlled monodispersity and morphology of particles without denaturation of bioactive molecules throughout the process, and this is possible with the use of emulsion. However, it has the potential to reduce or stop degradation of protein drugs and offer a strict control over particle morphology and size distribution. The principle of electrospray is based on the theory of charged droplets, 'stating that an electric field applied to a liquid droplet exiting a capillary is able to deform the interface of the droplet' [24]. Some literatures published state that electrospray is better than the other drying techniques because of its advantages as it does not require a high temperature, might use little or no emulsion also and may not need further drying. In a study [25], lysozyme as a model protein was encapsulated within biodegradable microparticles using coaxial electrospray and the authors concluded that electrospray could be a promising approach to encapsulate biomolecules [25]. Bock et al. have also done a review on electrospraying of polymer with therapeutic

**75**

**Figure 2.**

*Picture shows the spray-drying technique.*

*Effect of Spray-Drying and Electrospraying as Drying Techniques on Lysozyme Characterisation*

molecules as a state of the art and have concluded also that electrospraying technique may emerge as promising in the production of particles with entrapped therapeutic molecules that may be released as particle degradation occurs. So far, most of the research reports for electrospraying technique using proteins were based on using polymeric systems in order to encapsulate the protein either in protein carriers or nano- or microcapsules. For example, Suksamran et al. [26] successfully synthesised alginate microparticles (0.9–4 μm in diameter) with ~50% entrapment efficiency of bovine serum albumin that raised promises for oral drug delivery of proteins. Moreover, tristearin nanoparticles (∼100–300 nm in diameter) were developed to aid the delivery of angiotensin II alongside clear core-shell particles with ∼92 ± 1.8% encapsulation efficiency [27]. Electrosprayed core-shell microspheres (2–8 μm) with encapsulated bovine serum albumin as the core and an amphiphilic biodegradable polymer (poly(ε-caprolactone)-poly(aminoethyl ethylene phosphate) block copolymer) as the shell for protein delivery were generated by a single-step electrospraying. The protein release profiles of the microspheres exhibited steady release kinetics for a period of 3 weeks without a significant initial

Spray-drying is an established technology for the production of dried products from the liquid state. This method has gained increased interest in dry power formulation over the past decade, due to its potential simplicity, adaptability, scalability and cost-effectiveness [29, 30]. It is a method that has been studied in dry powder protein production involving the use of high temperature during the drying process. The principle of spray-drying method relies on atomisation of a drug solution that is pumped into a dry hot chamber in the form of droplets. By the influence of the heat, these droplets evaporate leading to dry solids in either powder, granules or agglomerated particles based on the chemical and physical properties of the feed in addition to the design of the used spray-dryer (**Figure 2**). One of the challenges of producing protein formulation utilising spray-drying method is the ability to destabilise the protein due to hot temperature and pressure during the production process com-

pared to electrospray which uses charges for drying.

*DOI: http://dx.doi.org/10.5772/intechopen.86237*

burst [28].

*1.5.2 Spray-drying*

**Figure 1.** *Picture shows electrospray technique.*

#### *Effect of Spray-Drying and Electrospraying as Drying Techniques on Lysozyme Characterisation DOI: http://dx.doi.org/10.5772/intechopen.86237*

molecules as a state of the art and have concluded also that electrospraying technique may emerge as promising in the production of particles with entrapped therapeutic molecules that may be released as particle degradation occurs. So far, most of the research reports for electrospraying technique using proteins were based on using polymeric systems in order to encapsulate the protein either in protein carriers or nano- or microcapsules. For example, Suksamran et al. [26] successfully synthesised alginate microparticles (0.9–4 μm in diameter) with ~50% entrapment efficiency of bovine serum albumin that raised promises for oral drug delivery of proteins. Moreover, tristearin nanoparticles (∼100–300 nm in diameter) were developed to aid the delivery of angiotensin II alongside clear core-shell particles with ∼92 ± 1.8% encapsulation efficiency [27]. Electrosprayed core-shell microspheres (2–8 μm) with encapsulated bovine serum albumin as the core and an amphiphilic biodegradable polymer (poly(ε-caprolactone)-poly(aminoethyl ethylene phosphate) block copolymer) as the shell for protein delivery were generated by a single-step electrospraying. The protein release profiles of the microspheres exhibited steady release kinetics for a period of 3 weeks without a significant initial burst [28].

#### *1.5.2 Spray-drying*

*Electrospinning and Electrospraying - Techniques and Applications*

**1.5 Drying techniques**

*1.5.1 Electrohydrodynamic atomisation*

contain amine groups (NH2) with sugar and side chains of sugar. Addition of water molecules to the sugar linkage causes lysozyme to degrade the polysaccharide, thereby causing it to break open. Its activity is a function of the ionic strength and pH. It is active between a pH of 6.0 and pH 9.0. Maximum activity is observed at a pH of 6.2 and ionic strength 0.02–0.100 M compared to 0.01–0.06 M at pH 9.2.

EHDA also known as electrospray is a drying technique used in the production of dry powder with the help of charges. It was first observed and recorded by Williams Gilbert in 1600 [22]. It is a process where a liquid imposes through a nozzle (which is connected to a voltage supply) at a certain flow rate, subjecting to high potential electric field. As a result, the meniscus is elongated to form a jet that breaks up into droplet under electrical force influence. Particles can then be collected at a collecting platform that is located ~20 cm under the spraying nozzle (**Figure 1**). Various spraying modes can be obtained depending on the strength of the electric stress and on the kinetic energy of the liquid leaving the nozzle for nanoparticle production. It is a well-practised technique for generating very fine droplets with monodispersed size from the liquid under the influence of electric forces [23]. It can achieve controlled monodispersity and morphology of particles without denaturation of bioactive molecules throughout the process, and this is possible with the use of emulsion. However, it has the potential to reduce or stop degradation of protein drugs and offer a strict control over particle morphology and size distribution. The principle of electrospray is based on the theory of charged droplets, 'stating that an electric field applied to a liquid droplet exiting a capillary is able to deform the interface of the droplet' [24]. Some literatures published state that electrospray is better than the other drying techniques because of its advantages as it does not require a high temperature, might use little or no emulsion also and may not need further drying. In a study [25], lysozyme as a model protein was encapsulated within biodegradable microparticles using coaxial electrospray and the authors concluded that electrospray could be a promising approach to encapsulate biomolecules [25]. Bock et al. have also done a review on electrospraying of polymer with therapeutic

**74**

**Figure 1.**

*Picture shows electrospray technique.*

Spray-drying is an established technology for the production of dried products from the liquid state. This method has gained increased interest in dry power formulation over the past decade, due to its potential simplicity, adaptability, scalability and cost-effectiveness [29, 30]. It is a method that has been studied in dry powder protein production involving the use of high temperature during the drying process. The principle of spray-drying method relies on atomisation of a drug solution that is pumped into a dry hot chamber in the form of droplets. By the influence of the heat, these droplets evaporate leading to dry solids in either powder, granules or agglomerated particles based on the chemical and physical properties of the feed in addition to the design of the used spray-dryer (**Figure 2**). One of the challenges of producing protein formulation utilising spray-drying method is the ability to destabilise the protein due to hot temperature and pressure during the production process compared to electrospray which uses charges for drying.

**Figure 2.** *Picture shows the spray-drying technique.*

Various reports documented the use of spray-drying that produced protein formulations with high protein activity. For instance, the fabrication of uniform trehalose microparticles immobilised with trypsin showed ~97.7 ± 2.6% biological activity using an optimal trypsin/trehalose mass ratio of 1:1 [31]. Insulin microparticles were also designed by spray-drying method to bypass deposition in the extrathoracic region (mouth-throat). The total lung dose of >95% was achieved indicating a high degree of lung targeting [32]. Newly developed microencapsulated solid lipid nanoparticles containing papain (as a model protein) were prepared by spray-drying method. Papain was adsorbed onto glyceryl dibehenate and glyceryl tristearate solid lipid nanoparticle. The protein was found to be released from the particles to a large extent. Moreover, protein stability was reserved throughout spray-dried microsphere production [33].

This chapter aims to describe the effect of spray-dried and electrospray-dried formulations on lysozyme with and without excipients using various characterisation techniques like differential scanning calorimetry (DSC) to determine the thermal stability with lysozyme solid samples, UV-Vis spectroscopy for the enzymatic activity, dynamic light scattering for particle size, scanning electron microscope (SEM) for morphology of the particles and high-sensitivity DSC for thermal stability using lysozyme solutions and two drying (electrospray and spray-drying) techniques, to dry powders for characterisation.

#### **2. Materials and methods**

#### **2.1 Materials**

Chicken egg white lysozyme in lyophilised powder (90%), ethanol, *Micrococcus lysodeikticus* and betacyclodextrin were purchased from Sigma-Aldrich Chemicals Company. Sodium phosphate monobasic anhydrous, disodium hydrogen orthophosphate anhydrous and sodium chloride were obtained from Fisher Scientific Company.

#### **2.2 Methods**

#### *2.2.1 Preparation of spray-dried protein*

Aqueous lysozyme solutions (1% w/v) were spray-dried without and with an excipient (betacyclodextrin) via a BÜCHI Mini Spray Dryer B-290. Excipients were used at the concentrations of 1% w/v. The protein solution run through a silicone tubing of inner diameter of 4 mm, peristaltic feed pump (35%) to an 0.5 mm diameter atomising nozzle at rate of 20 ml/min and compressed air at rate of 600 l/h. In a glass chamber, protein solutions were sprayed at an inlet temperature of 130 ± 3°C, and outlet temperature was 73 ± 4°C. To minimise the effect of heat stress on the protein, a cooling water was distributed through a jacket around the nozzle. Spraydried protein powder were collected by a high-performance cyclone separator and stored in glass vials at 3–4°C.

#### *2.2.2 Preparation of electrosprayed lysozyme*

Lysozyme solutions (1% w/v) were prepared using (80/20 v/v) ethanol/water. Electrosprayed formulations were prepared without and with excipients (1% w/w of betacyclodextrin). A syringe containing 5 ml of the protein solution was attached to a syringe infusion pump (Harvard Apparatus, Pump 11 Elite, USA) attached

**77**

*Effect of Spray-Drying and Electrospraying as Drying Techniques on Lysozyme Characterisation*

to a high-power voltage supply (Glassman High Voltage Supply, UK). The protein solution was run through a silicone tubing attached to a stainless steel needle (inner diameter 0.3 cm) at a flow rates of 15 μL/min. Atomised particles were collected on microscope slides which fitted 20 cm below the tip of the nozzle. A high voltage was used to maintain the voltage range of 9–18 kV. The electrospraying process was

Microscopic examination of spray-dried and electrosprayed formulations was investigated utilising scanning electron microscope (SEM) (Hitachi S3000-N variable pressure scanning electron microscope, Japan). Around 2–3 mg of dried lysozyme formulations were applied to a double-sided carbon tape (Agar Scientific, Stansted, UK), fixed on an aluminium stub. The dried powder was sputter coated with a mixture of gold/palladium using a Quorum Technology (Polaron Range)

The thermal stability of lysozyme, before and after processing, was evaluated in the solid form using DSC Q1000M TA instrument, England. Pure indium standard was utilised to calibrate the DSC instrument. Unprocessed, spray-dried and electrosprayed formulation (2–3 mg) was sealed in a DSC aluminium pan with lids and loaded under nitrogen at a flow rate of 50 ml/min. An empty sealed pan was used as a reference. Pans were scanned in the range of 0–300°C at a rate of 10.0°C/min.

High-sensitivity DSC also known as VP-DSC was used in this study to determine the thermal behaviour and folding reversibility of lysozyme. The fresh sample 5 mg of each formulation (1 ml 0.1 M phosphate buffer at a pH of 6.24) and reference (0.1 M sodium phosphate buffer at a PH of 6.24) was degassed and injected into the cells using a syringe. The sample and reference were complete for maintenance of equal volumes, and the same amount of lysozyme was used in each run. The sample and reference were heated between 20 and 90°C at 1°C/min under pressure. The folding reversibility each, of the denatured protein, was evaluated by cycling temperature by carrying out three scans (up scan, 20–90°C; down scan, 90–20°C; and another up scan, 20–90°C). These engaged two or more scans at different temperatures. Furthermore, before the measurement of each sample, a baseline was run by loading both cells (sample and reference cells) with the reference; the baseline was later subtracted from the protein thermal data using the MicroCal VP-DSC, USA. The sample was analysed with Origin DSC analysis software by normalising the concentration and excesses in heat capacity. The calorimetric enthalpy changes which is the area under the peak (ΔH) and midpoint of the transition peak (*Tm*) were calculated.

Utilising M501 Single Beam Scanning UV/Visible Spectrophotometer Camspec (Biochrom, UK), the enzymatic activity of lysozyme was investigated by determining the hydrolysis rate of β-1,4-glycosidic linkages between N-acetylglucosamine and N-acetylmuramic acid in bacterial cell walls. Following a procedure described

mbar.

*DOI: http://dx.doi.org/10.5772/intechopen.86237*

conducted at ambient temperature (23°C).

*2.2.3.2 Differential scanning calorimetry (DSC)*

*2.2.3.4 Biological activity analysis of lysozyme*

*2.2.3.1 Scanning electron microscopy*

*2.2.3 Characterisation of spray-dried and electrosprayed lysozyme*

SC760 by subjecting powder to an argon atmosphere at about 10<sup>−</sup><sup>1</sup>

*2.2.3.3 High-sensitivity differential scanning calorimetry (HSDSC)*

*Effect of Spray-Drying and Electrospraying as Drying Techniques on Lysozyme Characterisation DOI: http://dx.doi.org/10.5772/intechopen.86237*

to a high-power voltage supply (Glassman High Voltage Supply, UK). The protein solution was run through a silicone tubing attached to a stainless steel needle (inner diameter 0.3 cm) at a flow rates of 15 μL/min. Atomised particles were collected on microscope slides which fitted 20 cm below the tip of the nozzle. A high voltage was used to maintain the voltage range of 9–18 kV. The electrospraying process was conducted at ambient temperature (23°C).

#### *2.2.3 Characterisation of spray-dried and electrosprayed lysozyme*

#### *2.2.3.1 Scanning electron microscopy*

*Electrospinning and Electrospraying - Techniques and Applications*

spray-dried microsphere production [33].

techniques, to dry powders for characterisation.

**2. Materials and methods**

*2.2.1 Preparation of spray-dried protein*

stored in glass vials at 3–4°C.

*2.2.2 Preparation of electrosprayed lysozyme*

**2.1 Materials**

Company.

**2.2 Methods**

Various reports documented the use of spray-drying that produced protein formulations with high protein activity. For instance, the fabrication of uniform trehalose microparticles immobilised with trypsin showed ~97.7 ± 2.6% biological activity using an optimal trypsin/trehalose mass ratio of 1:1 [31]. Insulin microparticles were also designed by spray-drying method to bypass deposition in the extrathoracic region (mouth-throat). The total lung dose of >95% was achieved indicating a high degree of lung targeting [32]. Newly developed microencapsulated solid lipid nanoparticles containing papain (as a model protein) were prepared by spray-drying method. Papain was adsorbed onto glyceryl dibehenate and glyceryl tristearate solid lipid nanoparticle. The protein was found to be released from the particles to a large extent. Moreover, protein stability was reserved throughout

This chapter aims to describe the effect of spray-dried and electrospray-dried formulations on lysozyme with and without excipients using various characterisation techniques like differential scanning calorimetry (DSC) to determine the thermal stability with lysozyme solid samples, UV-Vis spectroscopy for the enzymatic activity, dynamic light scattering for particle size, scanning electron microscope (SEM) for morphology of the particles and high-sensitivity DSC for thermal stability using lysozyme solutions and two drying (electrospray and spray-drying)

Chicken egg white lysozyme in lyophilised powder (90%), ethanol, *Micrococcus lysodeikticus* and betacyclodextrin were purchased from Sigma-Aldrich Chemicals Company. Sodium phosphate monobasic anhydrous, disodium hydrogen orthophosphate anhydrous and sodium chloride were obtained from Fisher Scientific

Aqueous lysozyme solutions (1% w/v) were spray-dried without and with an excipient (betacyclodextrin) via a BÜCHI Mini Spray Dryer B-290. Excipients were used at the concentrations of 1% w/v. The protein solution run through a silicone tubing of inner diameter of 4 mm, peristaltic feed pump (35%) to an 0.5 mm diameter atomising nozzle at rate of 20 ml/min and compressed air at rate of 600 l/h. In a glass chamber, protein solutions were sprayed at an inlet temperature of 130 ± 3°C, and outlet temperature was 73 ± 4°C. To minimise the effect of heat stress on the protein, a cooling water was distributed through a jacket around the nozzle. Spraydried protein powder were collected by a high-performance cyclone separator and

Lysozyme solutions (1% w/v) were prepared using (80/20 v/v) ethanol/water. Electrosprayed formulations were prepared without and with excipients (1% w/w of betacyclodextrin). A syringe containing 5 ml of the protein solution was attached to a syringe infusion pump (Harvard Apparatus, Pump 11 Elite, USA) attached

**76**

Microscopic examination of spray-dried and electrosprayed formulations was investigated utilising scanning electron microscope (SEM) (Hitachi S3000-N variable pressure scanning electron microscope, Japan). Around 2–3 mg of dried lysozyme formulations were applied to a double-sided carbon tape (Agar Scientific, Stansted, UK), fixed on an aluminium stub. The dried powder was sputter coated with a mixture of gold/palladium using a Quorum Technology (Polaron Range) SC760 by subjecting powder to an argon atmosphere at about 10<sup>−</sup><sup>1</sup> mbar.

#### *2.2.3.2 Differential scanning calorimetry (DSC)*

The thermal stability of lysozyme, before and after processing, was evaluated in the solid form using DSC Q1000M TA instrument, England. Pure indium standard was utilised to calibrate the DSC instrument. Unprocessed, spray-dried and electrosprayed formulation (2–3 mg) was sealed in a DSC aluminium pan with lids and loaded under nitrogen at a flow rate of 50 ml/min. An empty sealed pan was used as a reference. Pans were scanned in the range of 0–300°C at a rate of 10.0°C/min.

#### *2.2.3.3 High-sensitivity differential scanning calorimetry (HSDSC)*

High-sensitivity DSC also known as VP-DSC was used in this study to determine the thermal behaviour and folding reversibility of lysozyme. The fresh sample 5 mg of each formulation (1 ml 0.1 M phosphate buffer at a pH of 6.24) and reference (0.1 M sodium phosphate buffer at a PH of 6.24) was degassed and injected into the cells using a syringe. The sample and reference were complete for maintenance of equal volumes, and the same amount of lysozyme was used in each run. The sample and reference were heated between 20 and 90°C at 1°C/min under pressure. The folding reversibility each, of the denatured protein, was evaluated by cycling temperature by carrying out three scans (up scan, 20–90°C; down scan, 90–20°C; and another up scan, 20–90°C). These engaged two or more scans at different temperatures. Furthermore, before the measurement of each sample, a baseline was run by loading both cells (sample and reference cells) with the reference; the baseline was later subtracted from the protein thermal data using the MicroCal VP-DSC, USA. The sample was analysed with Origin DSC analysis software by normalising the concentration and excesses in heat capacity. The calorimetric enthalpy changes which is the area under the peak (ΔH) and midpoint of the transition peak (*Tm*) were calculated.

#### *2.2.3.4 Biological activity analysis of lysozyme*

Utilising M501 Single Beam Scanning UV/Visible Spectrophotometer Camspec (Biochrom, UK), the enzymatic activity of lysozyme was investigated by determining the hydrolysis rate of β-1,4-glycosidic linkages between N-acetylglucosamine and N-acetylmuramic acid in bacterial cell walls. Following a procedure described

by Haj Ahmad et al. [34], the activity of lysozyme was assessed. A 100 ml of *Micrococcus lysodeikticus* suspension was prepared by adding 20 mg of the bacteria added to 10 ml of 1% sodium chloride solution and 90 ml of potassium phosphate buffer 0.067 M, pH 6.6. The biological reaction of lysozyme was initiated by adding 0.5 ml of protein solution (1.5 μg/ml), prepared using the same buffer, to 5 ml of the bacterial suspension. The unit activity of the protein was monitored by measuring the reduction rate in the absorbance at 450 nm. The biological activity of lysozyme was assessed using the equation suggested by Shugar [35]:

Activity (units/mg) = ∆450nm/min/0.001 × mg enzyme present in the mixture. (1)

#### *2.2.3.5 Particle size distribution analysis*

The particle size distribution of the dried particles was determined by dynamic light scattering technique using the Malvern Zetasizer (Nano ZSP, Malvern Instruments, UK). The particles were dispersed in ethanol containing 0.1% Tween® 80, which was selected to achieve suitable deagglomeration. The average particle size was measured at a scattering angle of 90° in three replicates for each sample.

#### **3. Results and discussion**

#### **3.1 Determination of percentage yields for spray-dried and electrosprayed lysozyme**

**Table 1** shows the percentage yield of the spray-dried and electrosprayed lysozyme formulation collected. For spray-dried lysozyme, 29% of the preparation was achieved. The percentage yield was higher (~53%) for spray-dried lysozyme with betacyclodextrin compared to the spray-dried lysozyme in the absence of excipient. The addition of betacyclodextrin reduced the deposition of spray-dried lysozyme on the wall of the spray-drying chamber and cyclone separator. With no significant differences, lysozyme formulation produced with electrospraying produced ~30%. However, a major reduction was noticed for electrospraying lysozyme with betacyclodextrin (~25%). Around 30–40% of product yield is typically expected for spray-drying formulations utilising benchtop spraying system [36]. Increasing the percentage yield can be achieved by introducing polymeric excipients with high glass transition temperature in addition to optimise the drying condition used during the spray-drying [37]. A largescale production is feasible in pharmaceutical industries for spray-drying formulations by using a large scalable spray-drier that would generate the highest possible yield [38]. This is also feasible for electrospraying by using, for example, a multi-tip emitter to improve the potential upscale electrospraying [39]. For electrospraying technique, the process parameters, such as feeding flow rate, voltage supply and the distance between the tip of the nozzle and the collecting platform, would affect the physical properties of the produced particles. It's worth mentioning that the time consumed by each process to generate the quantity outlined in **Table 1** was significantly different. Spray-drying process required 15–20 min for the whole sample, while more than 6 h was consumed to finish with all of the electrosprayed sample.

#### **3.2 Microscopic examination of spray-dried and electrosprayed protein particles**

**Figure 3** and **Table 1** show the SEM images and particle size of spray-dried and electrosprayed formulations, respectively. The process of protein preparation

**79**

*Effect of Spray-Drying and Electrospraying as Drying Techniques on Lysozyme Characterisation*

SD lysozyme 29 90.1 72.46 ± 0.38 201.30 2.3+ 0.06 ESR lysozyme 30 113 74.44 ± 0.22 222.18 1.6 ± 0.19

53 87.06 74.36 ± 0.26 No

25 100 74.51 ± 0.52 223.26 3.0 ± 0.91

**Tm (°C)a Apparent** 

100 74.32 ± 0.16 199.06 1.4 ± 0.04

**Tm (°C)b**

transition detected

**Mean diameter (μm) (mean ± SD)**

2.7 ± 0.5

**Biological activity (%)**

had a significant impact on the morphology and size of the spray-dried and electrosprayed lysozyme particles. As a result, it will impact the choice of the protein delivery system and route of drug administration. Protein particles produced by spray-drying technique were smooth and spherical in shape (**Figure 3A**) with a size of 2.3 + 0.06 μm, while mainly rodlike shape particles with few spherical particles were produced via electrospraying process (1.6 ± 0.19 μm). The inclusion of betacyclodextrin had no significant effect on the shape of electrosprayed particles (3.0 ± 0.91 μm), while solid dimple spheres were observed for spray-dried lysozyme with betacyclodextrin formulation (2.7 ± 0.5 μm) (**Figure 3**). For spray-drying process, Prinn et al. [40] suggested four categories to classify the morphology of the spray-dried particles: (I) smooth spheres, (II) dimpled or collapsed particles, (III) raisin like particles and (IV) highly crumpled folded particles. Accordingly, spraydried lysozyme without betacyclodextrin would fall into class I, and spray-dried lysozyme with betacyclodextrin would fall into class II. The rate of drying has a crucial impact on the morphology of the spray-dried particles; faster drying would result in more dimpled particles [41]. However, the spherical shape of the particles will not guaranty a 100% biological activity as will be discussed below. Moreover, it has been recognised that the optimal aerodynamic particle size distribution of particles intended for pulmonary delivery should be within the range of 1–5 μm [42]. Accordingly, all particles produced in this research would fit within this range and

*Shows percentage (%) yield, biological activity, denaturation temperature, Tm and particle size of dried* 

The electrospraying configuration used in this study consists of one conducting needle, and one voltage was applied. A stable Taylor cone usually forms at the tip of the needle generating nearly uniform particles with distinct morphology. The incorporated protein disperses equally with the solution (without and with the excipient) improving the amorphous nature and bioavailability (Mehta et al. [22]). Flow rate is highly related to the particle size of the electrosprayed particles. It documented that larger flow rates tend to generate smaller particle size [43]. The flow rate used in this study considered as low flow rate that might explain the large particle size of electrosprayed lysozyme especially with betacyclodextrin (**Table 1**, **Figure 3**). Also, a study conducted by Gomez et al. [44], electrospraying of insulin, suggested reducing protein concentration in the

*DOI: http://dx.doi.org/10.5772/intechopen.86237*

**(%) yield**

**Formulation Percentage** 

Unprocessed lysozyme

SD (1:1 w/w) lysozyme with betacyclodextrin

ESR (1:1 w/w) lysozyme with betacyclodextrin

*For aqueous protein formulations.*

*For solid protein formulations. SD, spray-dried; ESR, electrosprayed*

*a*

*b*

**Table 1.**

*lysozyme particles.*

thus are suitable for pulmonary delivery.

*Effect of Spray-Drying and Electrospraying as Drying Techniques on Lysozyme Characterisation DOI: http://dx.doi.org/10.5772/intechopen.86237*


*For solid protein formulations.*

*SD, spray-dried; ESR, electrosprayed*

#### **Table 1.**

*Electrospinning and Electrospraying - Techniques and Applications*

was assessed using the equation suggested by Shugar [35]:

was consumed to finish with all of the electrosprayed sample.

**3.2 Microscopic examination of spray-dried and electrosprayed protein** 

**Figure 3** and **Table 1** show the SEM images and particle size of spray-dried and electrosprayed formulations, respectively. The process of protein preparation

*2.2.3.5 Particle size distribution analysis*

**3. Results and discussion**

**lysozyme**

by Haj Ahmad et al. [34], the activity of lysozyme was assessed. A 100 ml of *Micrococcus lysodeikticus* suspension was prepared by adding 20 mg of the bacteria added to 10 ml of 1% sodium chloride solution and 90 ml of potassium phosphate buffer 0.067 M, pH 6.6. The biological reaction of lysozyme was initiated by adding 0.5 ml of protein solution (1.5 μg/ml), prepared using the same buffer, to 5 ml of the bacterial suspension. The unit activity of the protein was monitored by measuring the reduction rate in the absorbance at 450 nm. The biological activity of lysozyme

Activity (units/mg) = ∆450nm/min/0.001 × mg enzyme present in the mixture. (1)

The particle size distribution of the dried particles was determined by dynamic

Instruments, UK). The particles were dispersed in ethanol containing 0.1% Tween® 80, which was selected to achieve suitable deagglomeration. The average particle size was measured at a scattering angle of 90° in three replicates for each sample.

light scattering technique using the Malvern Zetasizer (Nano ZSP, Malvern

**3.1 Determination of percentage yields for spray-dried and electrosprayed** 

**Table 1** shows the percentage yield of the spray-dried and electrosprayed lysozyme formulation collected. For spray-dried lysozyme, 29% of the preparation was achieved. The percentage yield was higher (~53%) for spray-dried lysozyme with betacyclodextrin compared to the spray-dried lysozyme in the absence of excipient. The addition of betacyclodextrin reduced the deposition of spray-dried lysozyme on the wall of the spray-drying chamber and cyclone separator. With no significant differences, lysozyme formulation produced with electrospraying produced ~30%. However, a major reduction was noticed for electrospraying lysozyme with betacyclodextrin (~25%). Around 30–40% of product yield is typically expected for spray-drying formulations utilising benchtop spraying system [36]. Increasing the percentage yield can be achieved by introducing polymeric excipients with high glass transition temperature in addition to optimise the drying condition used during the spray-drying [37]. A largescale production is feasible in pharmaceutical industries for spray-drying formulations by using a large scalable spray-drier that would generate the highest possible yield [38]. This is also feasible for electrospraying by using, for example, a multi-tip emitter to improve the potential upscale electrospraying [39]. For electrospraying technique, the process parameters, such as feeding flow rate, voltage supply and the distance between the tip of the nozzle and the collecting platform, would affect the physical properties of the produced particles. It's worth mentioning that the time consumed by each process to generate the quantity outlined in **Table 1** was significantly different. Spray-drying process required 15–20 min for the whole sample, while more than 6 h

**78**

**particles**

*Shows percentage (%) yield, biological activity, denaturation temperature, Tm and particle size of dried lysozyme particles.*

had a significant impact on the morphology and size of the spray-dried and electrosprayed lysozyme particles. As a result, it will impact the choice of the protein delivery system and route of drug administration. Protein particles produced by spray-drying technique were smooth and spherical in shape (**Figure 3A**) with a size of 2.3 + 0.06 μm, while mainly rodlike shape particles with few spherical particles were produced via electrospraying process (1.6 ± 0.19 μm). The inclusion of betacyclodextrin had no significant effect on the shape of electrosprayed particles (3.0 ± 0.91 μm), while solid dimple spheres were observed for spray-dried lysozyme with betacyclodextrin formulation (2.7 ± 0.5 μm) (**Figure 3**). For spray-drying process, Prinn et al. [40] suggested four categories to classify the morphology of the spray-dried particles: (I) smooth spheres, (II) dimpled or collapsed particles, (III) raisin like particles and (IV) highly crumpled folded particles. Accordingly, spraydried lysozyme without betacyclodextrin would fall into class I, and spray-dried lysozyme with betacyclodextrin would fall into class II. The rate of drying has a crucial impact on the morphology of the spray-dried particles; faster drying would result in more dimpled particles [41]. However, the spherical shape of the particles will not guaranty a 100% biological activity as will be discussed below. Moreover, it has been recognised that the optimal aerodynamic particle size distribution of particles intended for pulmonary delivery should be within the range of 1–5 μm [42]. Accordingly, all particles produced in this research would fit within this range and thus are suitable for pulmonary delivery.

The electrospraying configuration used in this study consists of one conducting needle, and one voltage was applied. A stable Taylor cone usually forms at the tip of the needle generating nearly uniform particles with distinct morphology. The incorporated protein disperses equally with the solution (without and with the excipient) improving the amorphous nature and bioavailability (Mehta et al. [22]). Flow rate is highly related to the particle size of the electrosprayed particles. It documented that larger flow rates tend to generate smaller particle size [43]. The flow rate used in this study considered as low flow rate that might explain the large particle size of electrosprayed lysozyme especially with betacyclodextrin (**Table 1**, **Figure 3**). Also, a study conducted by Gomez et al. [44], electrospraying of insulin, suggested reducing protein concentration in the

#### **Figure 3.**

*SEM images for (A) spray-dried lysozyme, (B) spray-dried lysozyme with betacyclodextrin, (C) electrosprayed lysozyme and (D) electrosprayed lysozyme with betacyclodextrin.*

solvent or the flow rate in order to achieve a smaller particle size. A future study with various lysozyme concentrations and higher and lower flow rates will be conducted. The particle morphology of protein formulations and size play a crucial role in the aerodynamic properties and performance of aerosol applications. Smooth spherical particles are more preferred than other particle shapes as they might result in much lower aerodynamic particle diameter in comparison with dense particles.

#### **3.3 Differential scanning calorimetry (DSC)**

DSC determines the variation in heat flow between the protein sample and an empty sealed pan that was used as a reference cell. Throughout a thermal event in the protein preparation, the operation of the system will conduct heat to, or from, the protein sample pan to maintain an equal temperature in both sample and reference pans. Thermal profiles of unprocessed, spray-dried and electrosprayed lysozyme formulations without excipients are presented in **Figure 4**. This represents the heat flow as a function of temperature and illustrates the apparent denaturation temperature *Tm* values of all protein preparations (**Table 1**). In the DSC thermogram scans, two endothermic peaks can be observed. The first endothermic broad peak (~120°C) indicates that the preparations contain some amount of water [45, 46]. The second endothermic peak around ~199°C represents the apparent denaturation transition of the protein in which the peak maximum was considered the apparent denaturation temperature [21].

**81**

**Figure 4.**

*Effect of Spray-Drying and Electrospraying as Drying Techniques on Lysozyme Characterisation*

Spray-drying of lysozyme has improved the denaturation temperature of lysozyme by about 2°C as compared with unprocessed lysozyme (**Table 1**). However, this transition was not significant. The presence of betacyclodextrin within spraydried sample indicated an amorphous protein content as no peak was detected around 199°C; this was in contrast with other publications which showed transition for spray-dried lysozyme with betacyclodextrin. Around 22°C increase of the denaturation temperature of lysozyme was observed for electrosprayed protein without any excipient (**Table 1**, **Figure 4**). Moreover, electrospraying of lysozyme with betacyclodextrin led to an increase (by ~23°C) of the apparent protein denaturation temperature compared to the unprocessed lysozyme. The results for electrospraying formulations suggest an increase of lysozyme thermal stability as they exhibited increase in denaturation temperatures indicating the effect of the process and the excipient on the protein's integrity, and this is in consistent with the biological

HSDSC offers information about protein folding and stability by measuring the thermodynamic parameters in solution forms which have an impact on protein folding-unfolding transitions [47]. Subsequently, this method was used to assess the thermal stability of the prepared protein solutions after processing. **Table 1** displays the HSDSC results for denaturation temperature of unprocessed, spray-dried and electrosprayed lysozyme preparations. The results (**Table 1**) show that the transition temperature (*Tm*) of the spray-dried formulation in the absence of betacyclodextrin reveals lower thermal stability (*Tm* was ~72°C) than the unprocessed lysozyme and other formulations (*Tm* was ~74°C). Electrosprayed samples have maintained the thermal stability of the protein after processing (*Tm* was ~74°C). However, after 6 months of storage of electrosprayed samples in solid forms, it was noticed that those samples showed visible aggregates upon addition of aqueous solutions, while

spray-dried lysozyme samples were soluble in the aqueous solutions.

The most crucial parameter in any protein formulation is to maintain the biological activity of the protein. This will give an indication about the integrity, foldability and stability of the protein. Biological activity test was run for lysozyme

*DOI: http://dx.doi.org/10.5772/intechopen.86237*

activity results for freshly dried protein samples.

*DSC thermograms for unprocessed, spray-dried and electrosprayed lysozyme.*

**3.4 Biological activity of lysozyme**

*Effect of Spray-Drying and Electrospraying as Drying Techniques on Lysozyme Characterisation DOI: http://dx.doi.org/10.5772/intechopen.86237*

#### **Figure 4.**

*Electrospinning and Electrospraying - Techniques and Applications*

solvent or the flow rate in order to achieve a smaller particle size. A future study with various lysozyme concentrations and higher and lower flow rates will be conducted. The particle morphology of protein formulations and size play a crucial role in the aerodynamic properties and performance of aerosol applications. Smooth spherical particles are more preferred than other particle shapes as they might result in much lower aerodynamic particle diameter in comparison

*SEM images for (A) spray-dried lysozyme, (B) spray-dried lysozyme with betacyclodextrin, (C) electrosprayed* 

DSC determines the variation in heat flow between the protein sample and an empty sealed pan that was used as a reference cell. Throughout a thermal event in the protein preparation, the operation of the system will conduct heat to, or from, the protein sample pan to maintain an equal temperature in both sample and reference pans. Thermal profiles of unprocessed, spray-dried and electrosprayed lysozyme formulations without excipients are presented in **Figure 4**. This represents the heat flow as a function of temperature and illustrates the apparent denaturation temperature *Tm* values of all protein preparations (**Table 1**). In the DSC thermogram scans, two endothermic peaks can be observed. The first endothermic broad peak (~120°C) indicates that the preparations contain some amount of water [45, 46]. The second endothermic peak around ~199°C represents the apparent denaturation transition of the protein in which the peak maximum was considered

**80**

with dense particles.

**Figure 3.**

**3.3 Differential scanning calorimetry (DSC)**

*lysozyme and (D) electrosprayed lysozyme with betacyclodextrin.*

the apparent denaturation temperature [21].

*DSC thermograms for unprocessed, spray-dried and electrosprayed lysozyme.*

Spray-drying of lysozyme has improved the denaturation temperature of lysozyme by about 2°C as compared with unprocessed lysozyme (**Table 1**). However, this transition was not significant. The presence of betacyclodextrin within spraydried sample indicated an amorphous protein content as no peak was detected around 199°C; this was in contrast with other publications which showed transition for spray-dried lysozyme with betacyclodextrin. Around 22°C increase of the denaturation temperature of lysozyme was observed for electrosprayed protein without any excipient (**Table 1**, **Figure 4**). Moreover, electrospraying of lysozyme with betacyclodextrin led to an increase (by ~23°C) of the apparent protein denaturation temperature compared to the unprocessed lysozyme. The results for electrospraying formulations suggest an increase of lysozyme thermal stability as they exhibited increase in denaturation temperatures indicating the effect of the process and the excipient on the protein's integrity, and this is in consistent with the biological activity results for freshly dried protein samples.

HSDSC offers information about protein folding and stability by measuring the thermodynamic parameters in solution forms which have an impact on protein folding-unfolding transitions [47]. Subsequently, this method was used to assess the thermal stability of the prepared protein solutions after processing. **Table 1** displays the HSDSC results for denaturation temperature of unprocessed, spray-dried and electrosprayed lysozyme preparations. The results (**Table 1**) show that the transition temperature (*Tm*) of the spray-dried formulation in the absence of betacyclodextrin reveals lower thermal stability (*Tm* was ~72°C) than the unprocessed lysozyme and other formulations (*Tm* was ~74°C). Electrosprayed samples have maintained the thermal stability of the protein after processing (*Tm* was ~74°C). However, after 6 months of storage of electrosprayed samples in solid forms, it was noticed that those samples showed visible aggregates upon addition of aqueous solutions, while spray-dried lysozyme samples were soluble in the aqueous solutions.

#### **3.4 Biological activity of lysozyme**

The most crucial parameter in any protein formulation is to maintain the biological activity of the protein. This will give an indication about the integrity, foldability and stability of the protein. Biological activity test was run for lysozyme before and after processing. Solid protein samples were reconstituted, and the biological activity was expressed as a percentage that is relative to the control protein (activity of unprocessed protein was 100%). **Table 1** displays the biological activity results for spray-dried and electrosprayed lysozyme formulations. Spray-drying of lysozyme without and with betacyclodextrin led to about 10% reduction of lysozyme activity as compared with the unprocessed lysozyme. On the other hand, electrospraying of lysozyme better maintained protein biological activity compared to spray-dried protein formulations (**Table 1**). However, aggregate formation in solutions was noticed after 6 months of storage of electrosprayed lysozyme solid samples, meaning that proper storage conditions require to be maintained for longterm stability of dried lysozyme samples prepared by electrospraying technique.

The outcomes of this study could be explained on the basis that spray-drying process has perturbed the tertiary structure of lysozyme, thus reducing the biological activity of the protein; these results are in agreement with Haj Ahmad et al. [21] and Hulse et al. [45]. Lu et al. [48] reported that the type and percentage of the excipient used would influence the stability of protein formulation. The addition of betacyclodextrin to the spray-drying formulation did not have any improvement as ~87% biological activity of lysozyme was achieved. Sustaining the tertiary structure of lysozyme is critical for its full activity. One of the vital factors for this is the level of hydration at the active site cleft of the protein. Nagendra et al. [49] suggested that the active site in the lysozyme is heavily hydrated and ~0.2 grammes of water/g protein is required for the protein to maintain its biological activity with at least 9.4% of moisture content. Otherwise, the active site cleft will shrink, and thus the protein will inactivate [49]. On the other hand, 100% of the protein biological activity was observed for freshly electrosprayed lysozyme without and with betacyclodextrin suggesting the full hydration of the active site cleft in the protein. A study conducted by Gomez et al. [44] using insulin as a model protein reported electrospraying technique was gentle not to hinder the biological activity of insulin. The overall results suggest that different ways of drying (e.g. heating like in spray-drying and electric charge like in electrospraying) have different influences on the protein biological activity. The structure of proteins embraces several weak interactions (hydrogen bonging and electrostatic). These interactions can easily be affected by subjecting to physical and chemical stimuli that would include various processing conditions of conventional processing techniques (e.g. spray-drying) where high temperature or stress is applied. High temperature tends to denature sensitive biomolecules, such as proteins. Atomisation of materials by electrospraying relies mainly on evaporation of the solvent to generate dry particles without affecting the characteristics of proteins such as biological activity. While denaturation by the effect of temperature can be avoided, some denaturation and degradation might be initiated by the shear stress in the nozzle tip through which the aqueous solvent is infused [22, 37, 50, 51]. In this study, the biological activity of freshly dried lysozyme forms was conserved by using electrospraying method compared with spray-drying technique. However, aggregate formation in solutions was noticed after 6 months of storage of electrosprayed lysozyme solid samples, meaning that proper storage conditions require to be maintained for long-term stability of dried lysozyme samples prepared by electrospraying technique. Accordingly, there is a need for further study of the stability of the protein particles at various temperature and humidity conditions.

#### **4. Conclusion**

It was observed that electrospray lysozyme formulations without and with the used excipient looked promising compared to unprocessed and spray-dried

**83**

**Author details**

Ijeoma Abraham1

and Amal Ali Elkordy1

provided the original work is properly cited.

, Eman Ali Elkordy2

\*

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

1 School of Pharmacy and Pharmaceutical Science, University of Sunderland, UK

2 Faculty of Medicine, Imam Mohammad Ibn Saud Islamic University, Saudi Arabia

3 Leicester School of Pharmacy, De Montfort University, Leicester, UK

\*Address all correspondence to: amal.elkordy@sunderland.ac.uk

, Rita Haj Ahmad3

, Zeeshan Ahmad3

*Effect of Spray-Drying and Electrospraying as Drying Techniques on Lysozyme Characterisation*

formulations. However, it was observed that proper storage for electrosprayed samples is needed as the protein degraded after some time of storage. Spray-dry and electrospray seem to have some positive and negative effects on the lysozyme

This study was partially supported by EPSRC EHDA network for part funding

*DOI: http://dx.doi.org/10.5772/intechopen.86237*

**Acknowledgements**

depending on the technique and its used parameters.

and the ability to use the EHDA equipment for this research.

*Effect of Spray-Drying and Electrospraying as Drying Techniques on Lysozyme Characterisation DOI: http://dx.doi.org/10.5772/intechopen.86237*

formulations. However, it was observed that proper storage for electrosprayed samples is needed as the protein degraded after some time of storage. Spray-dry and electrospray seem to have some positive and negative effects on the lysozyme depending on the technique and its used parameters.

### **Acknowledgements**

*Electrospinning and Electrospraying - Techniques and Applications*

particles at various temperature and humidity conditions.

It was observed that electrospray lysozyme formulations without and with the used excipient looked promising compared to unprocessed and spray-dried

before and after processing. Solid protein samples were reconstituted, and the biological activity was expressed as a percentage that is relative to the control protein (activity of unprocessed protein was 100%). **Table 1** displays the biological activity results for spray-dried and electrosprayed lysozyme formulations. Spray-drying of lysozyme without and with betacyclodextrin led to about 10% reduction of lysozyme activity as compared with the unprocessed lysozyme. On the other hand, electrospraying of lysozyme better maintained protein biological activity compared to spray-dried protein formulations (**Table 1**). However, aggregate formation in solutions was noticed after 6 months of storage of electrosprayed lysozyme solid samples, meaning that proper storage conditions require to be maintained for longterm stability of dried lysozyme samples prepared by electrospraying technique. The outcomes of this study could be explained on the basis that spray-drying process has perturbed the tertiary structure of lysozyme, thus reducing the biological activity of the protein; these results are in agreement with Haj Ahmad et al. [21] and Hulse et al. [45]. Lu et al. [48] reported that the type and percentage of the excipient used would influence the stability of protein formulation. The addition of betacyclodextrin to the spray-drying formulation did not have any improvement as ~87% biological activity of lysozyme was achieved. Sustaining the tertiary structure of lysozyme is critical for its full activity. One of the vital factors for this is the level of hydration at the active site cleft of the protein. Nagendra et al. [49] suggested that the active site in the lysozyme is heavily hydrated and ~0.2 grammes of water/g protein is required for the protein to maintain its biological activity with at least 9.4% of moisture content. Otherwise, the active site cleft will shrink, and thus the protein will inactivate [49]. On the other hand, 100% of the protein biological activity was observed for freshly electrosprayed lysozyme without and with betacyclodextrin suggesting the full hydration of the active site cleft in the protein. A study conducted by Gomez et al. [44] using insulin as a model protein reported electrospraying technique was gentle not to hinder the biological activity of insulin. The overall results suggest that different ways of drying (e.g. heating like in spray-drying and electric charge like in electrospraying) have different influences on the protein biological activity. The structure of proteins embraces several weak interactions (hydrogen bonging and electrostatic). These interactions can easily be affected by subjecting to physical and chemical stimuli that would include various processing conditions of conventional processing techniques (e.g. spray-drying) where high temperature or stress is applied. High temperature tends to denature sensitive biomolecules, such as proteins. Atomisation of materials by electrospraying relies mainly on evaporation of the solvent to generate dry particles without affecting the characteristics of proteins such as biological activity. While denaturation by the effect of temperature can be avoided, some denaturation and degradation might be initiated by the shear stress in the nozzle tip through which the aqueous solvent is infused [22, 37, 50, 51]. In this study, the biological activity of freshly dried lysozyme forms was conserved by using electrospraying method compared with spray-drying technique. However, aggregate formation in solutions was noticed after 6 months of storage of electrosprayed lysozyme solid samples, meaning that proper storage conditions require to be maintained for long-term stability of dried lysozyme samples prepared by electrospraying technique. Accordingly, there is a need for further study of the stability of the protein

**82**

**4. Conclusion**

This study was partially supported by EPSRC EHDA network for part funding and the ability to use the EHDA equipment for this research.

#### **Author details**

Ijeoma Abraham1 , Eman Ali Elkordy2 , Rita Haj Ahmad3 , Zeeshan Ahmad3 and Amal Ali Elkordy1 \*

1 School of Pharmacy and Pharmaceutical Science, University of Sunderland, UK


\*Address all correspondence to: amal.elkordy@sunderland.ac.uk

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

### **References**

[1] Ohtake S, Yoshiko K, Arakawa T. Interactions of formulation excipients with proteins in solution and in dried state. Advanced Drug Delivery Reviews. 2011;**63**(13):1053-1073

[2] Lim H-P, Tey B-T, Chan E-S. Particle designs for the stabilisation and controlled-delivery of protein drugs by biopolymers: A case study on insulin. Journal of Controlled Release. 2014;**186**:11-21

[3] George CL. What is Protein? 1992. Available from: https://digitalcommons. usu.edu/cgi/viewcontent.cgi?article=161 2&context=extension\_histall [Accessed: March 6, 2019]

[4] Lesk MA. Introduction to Protein Science Architecture Function and Genomics. New York: Oxford University Press; 2004

[5] Cleland JL, Craik SC. Protein Engineering Principles and Practice. Canada: John Westley & Sons Publication; 1996. pp. 4-5

[6] Saito N, Kobayashi Y. The Physical Foundation of Protein Architecture. International Journal of Modern Physics B. 1999;**13**:2431-2529

[7] Elkordy AA, Forbes RT, Barry BW. Study of protein conformational stability and integrity using calorimetry and FT-Raman spectroscopy correlated with enzymatic activity. European Journal of Pharmaceutical Sciences. 2008;**33**(2):177-190

[8] Elkordy AA, Forbes RT, Barry BW. Integrity of crystalline lysozyme exceeds that of a spray-dried form. International Journal of Pharmaceutics. 2002;**247**:79-90

[9] Kocherbitov V, Arnebrant T. Hydration of thermally denatured lysozyme studied by sorption

calorimetry and differential scanning calorimetry. The Journal of Physical Chemistry. 2006;**110**:10144-10150

[10] Gill P, Moghadam TT, Ranjbar B. Differential scanning calorimetry technique: Application in biology and nanoscience. Journal of Biomolecular Techniques. 2010;**21**:167-193

[11] Privalov PL, Dragan AI. Microcalorimetry of biological macromolecules. Journal of Biophysical Chemistry. 2007;**126**:16-24

[12] Challener CA. Excipient selection for protein stabilization. The Journal of Pharmacy Technology. 2015;**3**:35-39

[13] Forbes RT, Barry BW, Elkordy AA. Preparation and characterisation of spray dried and crystallised trypsin: FT-Raman study to detect protein denaturation after thermal stresses. European Journal of Pharmaceutical Sciences. 2007;**30**:315-323

[14] Moggridge J, Biggar K, Dawson N, Storey KB. Sensitive detection of immunoglobulin G stability using in real-time isothermal differential scanning Fluorimetry: Determinants of protein stability for antibody-based therapeutics. Technology in Cancer Research & Treatment. 2017;**16**(6):997-1005. DOI: 10.1177/1533034617714149

[15] Siew A. Freeze-drying protein formulation. The Journal of Pharmacy Technology. 2014;**38**:5

[16] Amorij JP, Huckriede A, Wilschut J, Frijlink H, Hinrichs W. Development of stable influenza vaccine powder formulations: Challenges and possibilities. Pharmaceutical Research. 2008;**25**:1256-1273

[17] Chang LL, Pikal MJ. Mechanisms of protein stabilisation in the solid state. Journal of Pharmaceutical Sciences. 2009;**98**:2886-2908

**85**

*Effect of Spray-Drying and Electrospraying as Drying Techniques on Lysozyme Characterisation*

[26] Suksamran T, Opanasopit P, Rojanarata T, Ngawhirunpat T, Ruktanonchai U, Supaphol P. Biodegradable alginate microparticles developed by electrohydrodynamic spraying techniques for oral delivery of protein. Journal of Microencapsulation.

[27] Rasekh M, Young C, Roldo M, Lancien F, Le Mével J-C, Hafizi S, et al. Hollow-layered nanoparticles for therapeutic delivery of peptide prepared using electrospraying. Journal of Materials Science. Materials in

[28] Wu Y, Liao I-C, Kennedy SJ, Du J, Wang J, Leong KW, et al. Electrosprayed core-shell microspheres for protein delivery. Chemical Communications.

[29] Fourie P, Germishuizen W, Wong Y-L, Edwards D. Spray drying TB vaccines for pulmonary administration. Expert Opinion on Biological Therapy.

[30] Lee YY, Wu JX, Yang M, Young PM, van den Berg F, Rantanen J. Particle size dependence of polymorphism in spraydried mannitol. European Journal of Pharmaceutical Sciences. 2011;**44**:41-48

[31] Zhang S, Lei H, Gao X, Xiong X, Wu WD, Wu Z, et al. Fabrication of uniform enzyme-immobilized carbohydrate microparticles with high enzymatic activity and stability via spray drying and spray freeze drying. Powder Technology. 2018;**330**:40-49

[32] Ung KT, Rao N, Weers JG, Huang D, Chan HK. Design of spray dried insulin microparticles to bypass deposition in the extrathoracic region and maximize total lung dose. International Journal of Pharmaceutics. 2016;**511**(2):1070-1079

[33] Gasper DP, Serra C, Lino PR, Goncalves L, Taboada P, Remunan-Lopez C, et al. Microencapsulated SLN:

2009;**26**(7):563-570

Medicine. 2015;**26**:256

2010;**46**:4743-4745

2008;**8**:857-863

*DOI: http://dx.doi.org/10.5772/intechopen.86237*

preservation of lactobacillus acidophilus in saccharide matrices. Cryobiology.

[18] Conrad PB, Miller DP, Cielenski PR, de Pablo JJ. Stabilization and

[19] Vehring R. Pharmaceutical particle engineering via spray drying. Pharmaceutical Research.

[20] Ghaderi R, Carlfors J. Biological activity of lysozyme after entrapment in poly (d, l-lactide-co-glycolide) microspheres. Pharmaceutical Research

[21] Haj Ahmad R, Elkordy AA, Chaw CS, Moore A. Compare and contrast the effects of surfactants (Pluronic®F-127 and Cremophor®EL) and sugars

(β-cyclodextrin and inulin) on properties of spray dried and crystallised lysozyme. European Journal of Pharmaceutical

[23] Xie J, Jiang J, Davoodi P, Srinivasan MP, Wang CH. Electrohydrodynamic atomisation: A two-decade effort to produce and process micro−/ nano particulate materials. Chemical Engineering Science. 2015;**125**:32-57

[24] Bock N, Dargaville TR, Woodruff MA. Electro spraying of polymers with therapeutic molecules: State of the art. Progress in Polymer Science.

[25] Xie J, Ng WJ, Lee LY, Wang CH. Encapsulation of protein drugs in biodegradable microparticles by

co-axial electrospray. Journal of Colloid and Interface Science. 2008;**317**:469-476

Journal. 1997;**14**(11):1556-1562

Sciences. 2013;**49**(4):519-534

[22] Mehta P, Zaman A, Smith A, Rasekh M, Haj Ahmad R, Arshad MS, et al. Broad scale and structure fabrication of healthcare materials for drug and emerging therapies via electrohydrodynamic techniques. Advances in Therapy.

2018;**1800024**:1-27

2012;**37**:1510-1551

2000;**41**:17-24

2008;**25**:999-1022

*Effect of Spray-Drying and Electrospraying as Drying Techniques on Lysozyme Characterisation DOI: http://dx.doi.org/10.5772/intechopen.86237*

[18] Conrad PB, Miller DP, Cielenski PR, de Pablo JJ. Stabilization and preservation of lactobacillus acidophilus in saccharide matrices. Cryobiology. 2000;**41**:17-24

[19] Vehring R. Pharmaceutical particle engineering via spray drying. Pharmaceutical Research. 2008;**25**:999-1022

[20] Ghaderi R, Carlfors J. Biological activity of lysozyme after entrapment in poly (d, l-lactide-co-glycolide) microspheres. Pharmaceutical Research Journal. 1997;**14**(11):1556-1562

[21] Haj Ahmad R, Elkordy AA, Chaw CS, Moore A. Compare and contrast the effects of surfactants (Pluronic®F-127 and Cremophor®EL) and sugars (β-cyclodextrin and inulin) on properties of spray dried and crystallised lysozyme. European Journal of Pharmaceutical Sciences. 2013;**49**(4):519-534

[22] Mehta P, Zaman A, Smith A, Rasekh M, Haj Ahmad R, Arshad MS, et al. Broad scale and structure fabrication of healthcare materials for drug and emerging therapies via electrohydrodynamic techniques. Advances in Therapy. 2018;**1800024**:1-27

[23] Xie J, Jiang J, Davoodi P, Srinivasan MP, Wang CH. Electrohydrodynamic atomisation: A two-decade effort to produce and process micro−/ nano particulate materials. Chemical Engineering Science. 2015;**125**:32-57

[24] Bock N, Dargaville TR, Woodruff MA. Electro spraying of polymers with therapeutic molecules: State of the art. Progress in Polymer Science. 2012;**37**:1510-1551

[25] Xie J, Ng WJ, Lee LY, Wang CH. Encapsulation of protein drugs in biodegradable microparticles by co-axial electrospray. Journal of Colloid and Interface Science. 2008;**317**:469-476 [26] Suksamran T, Opanasopit P, Rojanarata T, Ngawhirunpat T, Ruktanonchai U, Supaphol P. Biodegradable alginate microparticles developed by electrohydrodynamic spraying techniques for oral delivery of protein. Journal of Microencapsulation. 2009;**26**(7):563-570

[27] Rasekh M, Young C, Roldo M, Lancien F, Le Mével J-C, Hafizi S, et al. Hollow-layered nanoparticles for therapeutic delivery of peptide prepared using electrospraying. Journal of Materials Science. Materials in Medicine. 2015;**26**:256

[28] Wu Y, Liao I-C, Kennedy SJ, Du J, Wang J, Leong KW, et al. Electrosprayed core-shell microspheres for protein delivery. Chemical Communications. 2010;**46**:4743-4745

[29] Fourie P, Germishuizen W, Wong Y-L, Edwards D. Spray drying TB vaccines for pulmonary administration. Expert Opinion on Biological Therapy. 2008;**8**:857-863

[30] Lee YY, Wu JX, Yang M, Young PM, van den Berg F, Rantanen J. Particle size dependence of polymorphism in spraydried mannitol. European Journal of Pharmaceutical Sciences. 2011;**44**:41-48

[31] Zhang S, Lei H, Gao X, Xiong X, Wu WD, Wu Z, et al. Fabrication of uniform enzyme-immobilized carbohydrate microparticles with high enzymatic activity and stability via spray drying and spray freeze drying. Powder Technology. 2018;**330**:40-49

[32] Ung KT, Rao N, Weers JG, Huang D, Chan HK. Design of spray dried insulin microparticles to bypass deposition in the extrathoracic region and maximize total lung dose. International Journal of Pharmaceutics. 2016;**511**(2):1070-1079

[33] Gasper DP, Serra C, Lino PR, Goncalves L, Taboada P, Remunan-Lopez C, et al. Microencapsulated SLN:

**84**

*Electrospinning and Electrospraying - Techniques and Applications*

calorimetry and differential scanning calorimetry. The Journal of Physical Chemistry. 2006;**110**:10144-10150

[10] Gill P, Moghadam TT, Ranjbar B. Differential scanning calorimetry technique: Application in biology and nanoscience. Journal of Biomolecular

Techniques. 2010;**21**:167-193

[11] Privalov PL, Dragan AI. Microcalorimetry of biological

Chemistry. 2007;**126**:16-24

Sciences. 2007;**30**:315-323

macromolecules. Journal of Biophysical

[12] Challener CA. Excipient selection for protein stabilization. The Journal of Pharmacy Technology. 2015;**3**:35-39

[13] Forbes RT, Barry BW, Elkordy AA. Preparation and characterisation of spray dried and crystallised trypsin: FT-Raman study to detect protein denaturation after thermal stresses. European Journal of Pharmaceutical

[14] Moggridge J, Biggar K, Dawson N, Storey KB. Sensitive detection of immunoglobulin G stability using in real-time isothermal differential scanning Fluorimetry: Determinants of protein stability for antibody-based therapeutics. Technology in Cancer Research

& Treatment. 2017;**16**(6):997-1005. DOI: 10.1177/1533034617714149

[15] Siew A. Freeze-drying protein formulation. The Journal of Pharmacy

[16] Amorij JP, Huckriede A, Wilschut J, Frijlink H, Hinrichs W. Development of stable influenza vaccine powder formulations: Challenges and

possibilities. Pharmaceutical Research.

[17] Chang LL, Pikal MJ. Mechanisms of protein stabilisation in the solid state. Journal of Pharmaceutical Sciences.

Technology. 2014;**38**:5

2008;**25**:1256-1273

2009;**98**:2886-2908

**References**

[1] Ohtake S, Yoshiko K, Arakawa

2011;**63**(13):1053-1073

2014;**186**:11-21

March 6, 2019]

Press; 2004

T. Interactions of formulation excipients with proteins in solution and in dried state. Advanced Drug Delivery Reviews.

[2] Lim H-P, Tey B-T, Chan E-S. Particle designs for the stabilisation and controlled-delivery of protein drugs by biopolymers: A case study on insulin. Journal of Controlled Release.

[3] George CL. What is Protein? 1992. Available from: https://digitalcommons. usu.edu/cgi/viewcontent.cgi?article=161 2&context=extension\_histall [Accessed:

[4] Lesk MA. Introduction to Protein Science Architecture Function and Genomics. New York: Oxford University

[5] Cleland JL, Craik SC. Protein Engineering Principles and Practice. Canada: John Westley & Sons Publication; 1996. pp. 4-5

[6] Saito N, Kobayashi Y. The Physical Foundation of Protein Architecture. International Journal of Modern Physics

[7] Elkordy AA, Forbes RT, Barry BW. Study of protein conformational stability and integrity using calorimetry and FT-Raman spectroscopy correlated with enzymatic activity. European Journal of Pharmaceutical Sciences.

[8] Elkordy AA, Forbes RT, Barry BW. Integrity of crystalline lysozyme exceeds that of a spray-dried form. International Journal of Pharmaceutics.

[9] Kocherbitov V, Arnebrant

T. Hydration of thermally denatured lysozyme studied by sorption

B. 1999;**13**:2431-2529

2008;**33**(2):177-190

2002;**247**:79-90

An innovative strategy for pulmonary protein delivery. International Journal of Pharmaceutics. 2017;**516**(1-2):231-246

[34] Haj Ahmad R, Chen YT, Elkordy A. An overview for the effects of lactitol, gelucire 44/14 and copovidone on lysozyme biological activity. European Journal of Biomedical and Pharmaceutical Sciences. 2015;**2**(3):1328-1339

[35] Shugar D. Measurement of lysozyme activity and ultraviolet inactivation of lysozyme. Biochimica et Biophysica Acta. 1952;**8**:302

[36] Hulse WL, Forbes RT, Bonner MC, Getrost M. Influence of protein on mannitol polymorphic form produced during co-spray drying. International Journal of Pharmaceutics. 2009;**382**(1-2):67-72

[37] Ziaee A, Albadarin AB, Padrela L, Femmer T, O'Reilly E, Walker G. Spray drying of pharmaceuticals and biopharmaceuticals: Critical parameters and experimental process optimization approaches. European Journal of Pharmaceutical Sciences. 2019;**127**:300-318

[38] Haj Ahmad R, Mamayusupov M, Elkordy EA, Elkordy AA. Influences of copolymers (Copovidone, Eudragit® RL PO and Kollicoat® MAE 30 DP) on stability and bioactivity of spraydried and freeze-dried lysozyme. Drug Development and Industrial Pharmacy. 2016;**42**(12):2086-2096

[39] Haj-Ahmad R, Rasekh M, Nazari K, Onaiwu EV, Yousef B, Morgan S, et al. Stable increased formulation atomization using a multi-tip nozzle device. Drug Delivery and Translational Research. 2018;**8**(6):1815-1827

[40] Prinn KB, Costantino HY, Tracy M. Statistical modelling of protein spray drying at the lab scale. AAPS PharmSciTech. 2002;**3**(1):E4

[41] Wang FJ, Wang CH. Effects of fabrication conditions on the characteristics of etanidazol spray-dried microspheres. Journal of Microencapsulation. 2002;**19**(4):495-510

[42] Hickey AJ. Pharmaceutical Inhalation Aerosol Technology. 2nd ed. In: Applications and Advances. CRC Press; 2016

[43] Almeria B, Deng W, Fahmy TM, Gomez A. Controlling the morphology of electrospray-generated PLGA microparticles for drug delivery. Journal of Colloid and Interface Science. 2010;**343**(1):125-133

[44] Gomez A, Bingham D, De Juan L, Tang K. Production of Protein Nanoparticles by Electrospraying; Journal of Aerosol Science. 1998;**29**:561-574

[45] Hulse LW, Forbes TR, Bonner CM, Getrost M. Do co-spray dried excipients offer better lysozyme stabilization than single excipients? European Journal of Pharmaceutical Sciences. 2008;**33**:294-305

[46] Kayaci F, Uyar T. Electrospun zein nanofibers in incorporating cyclodextrins. Carbohydrate Polymers. 2012;**90**:558-568

[47] Cooper A, Johnson CM. Chapter 10: Differential scanning calorimetry. In: Jones C, Mulloy B, Thomas AH, editors. Methods in Molecular Biology. Vol. 22: Microscopy, Optical Spectroscopy, and Macroscopic Techniques. Totowa, N.J: Humana Press; 1994. pp. 125-136

[48] Lu J, Wang X-J, Liu Y-X, Ching C-B. Thermal and FTIR investigation of freeze-dried protein-excipient mixtures. Journal of Thermal Analysis and Calorimetry. 2007;**89**(3):913-919

[49] Nagendra HG, sukumar N, Vijayan M. Role of water in plasticity,

**87**

*Effect of Spray-Drying and Electrospraying as Drying Techniques on Lysozyme Characterisation*

*DOI: http://dx.doi.org/10.5772/intechopen.86237*

stability, and action of proteins: The crystal structures of lysozyme at very low levels of hydration. Proteins Structure Function and Bioinformatics.

[50] Sridhar R, Lakshminarayanan R, Madhaiyan K, Barathi VA, Limh KHC, Ramakrishna S. Electrosprayed nanoparticles and electrospun

nanofibers based on natural materials: Applications in tissue regeneration, drug delivery and pharmaceuticals.

Chemical Society Reviews.

Journal. 2010;**28**:91-115

[51] Yurteri CU, Hartman RPA, Marijnissen JCM. Producing pharmaceutical particles via

electrospraying with an emphasis on nano and nano structured particles—A review. Kona Powder and Particle

1998;**32**:229-240

2015;(44):790

*Effect of Spray-Drying and Electrospraying as Drying Techniques on Lysozyme Characterisation DOI: http://dx.doi.org/10.5772/intechopen.86237*

stability, and action of proteins: The crystal structures of lysozyme at very low levels of hydration. Proteins Structure Function and Bioinformatics. 1998;**32**:229-240

*Electrospinning and Electrospraying - Techniques and Applications*

[41] Wang FJ, Wang CH. Effects of fabrication conditions on the characteristics of etanidazol spray-dried microspheres. Journal of Microencapsulation.

[42] Hickey AJ. Pharmaceutical

Inhalation Aerosol Technology. 2nd ed. In: Applications and Advances. CRC

[43] Almeria B, Deng W, Fahmy TM, Gomez A. Controlling the morphology of electrospray-generated PLGA

of Colloid and Interface Science.

[44] Gomez A, Bingham D, De Juan L, Tang K. Production of Protein Nanoparticles by Electrospraying; Journal of Aerosol Science.

[45] Hulse LW, Forbes TR, Bonner CM, Getrost M. Do co-spray dried excipients offer better lysozyme stabilization than single excipients? European Journal of Pharmaceutical Sciences.

[46] Kayaci F, Uyar T. Electrospun zein nanofibers in incorporating cyclodextrins. Carbohydrate Polymers.

[47] Cooper A, Johnson CM. Chapter 10: Differential scanning calorimetry. In: Jones C, Mulloy B, Thomas AH, editors. Methods in Molecular Biology. Vol. 22: Microscopy, Optical Spectroscopy, and Macroscopic Techniques. Totowa, N.J: Humana Press; 1994. pp. 125-136

[48] Lu J, Wang X-J, Liu Y-X, Ching C-B. Thermal and FTIR investigation of freeze-dried protein-excipient mixtures.

Journal of Thermal Analysis and Calorimetry. 2007;**89**(3):913-919

[49] Nagendra HG, sukumar N, Vijayan M. Role of water in plasticity,

2010;**343**(1):125-133

1998;**29**:561-574

2008;**33**:294-305

2012;**90**:558-568

microparticles for drug delivery. Journal

2002;**19**(4):495-510

Press; 2016

An innovative strategy for pulmonary protein delivery. International Journal of Pharmaceutics. 2017;**516**(1-2):231-246

[34] Haj Ahmad R, Chen YT, Elkordy A. An overview for the effects of lactitol, gelucire 44/14 and copovidone

[35] Shugar D. Measurement of lysozyme activity and ultraviolet inactivation of lysozyme. Biochimica et Biophysica

[36] Hulse WL, Forbes RT, Bonner MC, Getrost M. Influence of protein on mannitol polymorphic form produced during co-spray drying. International Journal of Pharmaceutics.

[37] Ziaee A, Albadarin AB, Padrela L, Femmer T, O'Reilly E, Walker G. Spray drying of pharmaceuticals and biopharmaceuticals: Critical parameters and experimental process optimization approaches. European Journal of Pharmaceutical Sciences.

[38] Haj Ahmad R, Mamayusupov M, Elkordy EA, Elkordy AA. Influences of copolymers (Copovidone, Eudragit® RL PO and Kollicoat® MAE 30 DP) on stability and bioactivity of spraydried and freeze-dried lysozyme. Drug Development and Industrial Pharmacy.

[39] Haj-Ahmad R, Rasekh M, Nazari K, Onaiwu EV, Yousef B, Morgan S, et al. Stable increased formulation atomization using a multi-tip nozzle device. Drug Delivery and Translational

[40] Prinn KB, Costantino HY, Tracy M. Statistical modelling of protein spray drying at the lab scale. AAPS PharmSciTech. 2002;**3**(1):E4

Research. 2018;**8**(6):1815-1827

on lysozyme biological activity. European Journal of Biomedical and Pharmaceutical Sciences.

2015;**2**(3):1328-1339

Acta. 1952;**8**:302

2009;**382**(1-2):67-72

2019;**127**:300-318

2016;**42**(12):2086-2096

**86**

[50] Sridhar R, Lakshminarayanan R, Madhaiyan K, Barathi VA, Limh KHC, Ramakrishna S. Electrosprayed nanoparticles and electrospun nanofibers based on natural materials: Applications in tissue regeneration, drug delivery and pharmaceuticals. Chemical Society Reviews. 2015;(44):790

[51] Yurteri CU, Hartman RPA, Marijnissen JCM. Producing pharmaceutical particles via electrospraying with an emphasis on nano and nano structured particles—A review. Kona Powder and Particle Journal. 2010;**28**:91-115

Chapter 5

Abstract

Using the iESP Installed on the

Irregular Gravitational Field of the

Olga Starinova, Andrey Shornikov and Elizaveta Nikolaeva

The gravitational field of asteroids and comets often has a complex dynamically changing shape. The study of the gravitational field of such bodies is essential for the design of missions, especially for missions involving maneuvering in close proximity, landing, and takeoff from the surface of a celestial body. This chapter deals to the problem of spacecraft's controlled motion near objects with irregular

gravitational fields. We propose to use a propulsion system based on ion electrospray propulsions (iESP), which usually used to control the spacecraft's motion relative to the mass center. The chapter describes the gravitational field of an asteroid as the superposition of the fields of two rotating point masses. The proposed control laws made it possible to stabilize the orbit near the asteroid surface. We performed the simulation of motion close to two relatively well-studied asteroids Eros and Gaspra. The results of the simulation demonstrated that the using of iESP as the auxiliary propulsion systems is sufficient to control the spacecraft's

Keywords: asteroid, boundary task, electric propulsion engine,

gravitational potential, n-body problem, spacecraft, iESP, electrospray engine

Over recent decades, there has been an increase in interest of the asteroids, comets, and other small celestial body studies. This is due to the changes in the research vector toward the solution of applied problems: counteraction to asteroids [1] and comet [2] hazards and development of small solar system objects with the

When designing research missions, there is a problem of the development of spacecraft control schemes in the attraction fields of complex geometric shapes bodies. The gravitational force between the elementary masses in that type of bodies is not sufficient to form the bodies in correct ellipsoidal or spheroidal form. Complex geometry creates the gravitational field of the complex configuration [1]. The spacecraft's behavior in this field is significantly different from the behavior of similar spacecraft near ellipsoidal and spheroidal bodies, the shape of which, as well as their gravitational field, can be considered correct in some approximation. The

motion in irregular gravitational fields.

purpose of mineral extraction [3, 4].

1. Introduction

89

Space Station Moving in an

Asteroids Eros and Gaspra

#### Chapter 5

## Using the iESP Installed on the Space Station Moving in an Irregular Gravitational Field of the Asteroids Eros and Gaspra

Olga Starinova, Andrey Shornikov and Elizaveta Nikolaeva

#### Abstract

The gravitational field of asteroids and comets often has a complex dynamically changing shape. The study of the gravitational field of such bodies is essential for the design of missions, especially for missions involving maneuvering in close proximity, landing, and takeoff from the surface of a celestial body. This chapter deals to the problem of spacecraft's controlled motion near objects with irregular gravitational fields. We propose to use a propulsion system based on ion electrospray propulsions (iESP), which usually used to control the spacecraft's motion relative to the mass center. The chapter describes the gravitational field of an asteroid as the superposition of the fields of two rotating point masses. The proposed control laws made it possible to stabilize the orbit near the asteroid surface. We performed the simulation of motion close to two relatively well-studied asteroids Eros and Gaspra. The results of the simulation demonstrated that the using of iESP as the auxiliary propulsion systems is sufficient to control the spacecraft's motion in irregular gravitational fields.

Keywords: asteroid, boundary task, electric propulsion engine, gravitational potential, n-body problem, spacecraft, iESP, electrospray engine

#### 1. Introduction

Over recent decades, there has been an increase in interest of the asteroids, comets, and other small celestial body studies. This is due to the changes in the research vector toward the solution of applied problems: counteraction to asteroids [1] and comet [2] hazards and development of small solar system objects with the purpose of mineral extraction [3, 4].

When designing research missions, there is a problem of the development of spacecraft control schemes in the attraction fields of complex geometric shapes bodies. The gravitational force between the elementary masses in that type of bodies is not sufficient to form the bodies in correct ellipsoidal or spheroidal form. Complex geometry creates the gravitational field of the complex configuration [1]. The spacecraft's behavior in this field is significantly different from the behavior of similar spacecraft near ellipsoidal and spheroidal bodies, the shape of which, as well as their gravitational field, can be considered correct in some approximation. The

modeling of spacecraft motion and the development of control schemes near asteroids and comets is possible only under the condition that those bodies gravitational field formalization task was solved with the prescribed accuracy. However, if we take into consideration cavities and voids in the object structure, the center of masses displacement, and the uneven distribution of density [5], it becomes difficult to solve the gravitational field formalization problem.

In addition to the high accuracy of the gravitational field model, the lightweight of the model plays a huge role in ballistic design. The task of the spacecraft motion modeling and the task of finding optimally sustainable control schemes are virtually non-solvable because of the overloaded model of gravitational potential. That is why the task is to find a balance between the accuracy of the object's potential appearance and the convergence property of the task.

The problem of finding the correct mathematical description of the gravitational fields of different shaped objects was addressed in a number of sources. For example, in the paper [6], the authors address the polygonal method of presenting the gravitational potential of asteroid 4769 Castalia as a formal model. A comparison of the proposed approach with the model of point attracting center takes place in the paper [7], where authors present a comparative analysis of the polygonal model and the model of point attracting center for the asteroid 216 Cleopatra. The paper [8] described and compared the gravitational potential presented in the form of series expanded into spherical, spheroidal, and ellipsoidal functions for Martian moons. In the paper [9], the authors address the position of equilibrium points for 23 different asteroids in their polygonal models of gravitational fields.

A number of mathematical methods can be used for deriving a model of an irregular gravitational field. This chapter suggests the model of gravitational potential based on the n-body problem. Authors developed the idea of superposition of single gravitate mass points potential. The problem is to determine the necessary number of mass points and to define their locations. It is considered that two gravity points suffice for the simulation of gravitational field. It should be noted that the model under consideration assume that the asteroid's density is distributed

Using the iESP Installed on the Space Station Moving in an Irregular Gravitational Field…

In the paper [15], authors compare the barycentrical form of gravitational potential and gravitational potential in spherical harmonic coefficients. It is proved

their vector positions (Figure 1). The corresponding form of the gravitational

Mass, kg 6.69 � <sup>10</sup><sup>15</sup> <sup>2</sup>–<sup>3</sup> � 1016 Density, kg/cm<sup>3</sup> 2.67 2.7

Dimensions, km 34.4 � 11.2 � 11.2 18.2 � 10.5 � 8.9 Mean diameter, km 16.84 12.2 Rotation period, hours 5.27 7.04

Eccentricity 0.22263 0.17363 Major axis, a.u. 1.45796 2.20971 Perihelion argument, deg 178.79567 129.72454 Inclination of orbit, deg 10.8289 4.10220 Circulation period, days 642.989 1199.782 Longitude of ascending node, deg 304.33453 253.17193

, <sup>r</sup><sup>2</sup> <sup>¼</sup> <sup>x</sup>2, y2, z<sup>2</sup>

are

that barycentric potential is accurate enough for the motion simulations.

Let M1, M<sup>2</sup> is masses of gravity points and r<sup>1</sup> ¼ x1; y1; z<sup>1</sup>

Physical characteristics of the asteroids 433 Eros and 951 Gaspra

Orbital characteristics of the asteroids 433 Eros and 951 Gaspra

Physical and orbital characteristics of the asteroids 433 Eros and 951 Gaspra.

Table 1.

91

Figure 1.

evenly throughout the body to simplify the calculations.

Asteroid Eros 433 as a superposition of two rotation mass points.

DOI: http://dx.doi.org/10.5772/intechopen.85615

potential Ux, y, <sup>z</sup> for this case is taken from [16]:

The drawbacks of the approaches addressed are their cumbersomeness when using in the problems of spacecraft flight dynamics and the necessity to know in advance the physical properties of the objects—geometry and mass distribution. Modeling the gravitational field of objects whose properties and structure are not known in advance within the models described is not possible.

This work analyzes the possibility of using ion electrospray propulsions to stabilize the orbit of a spacecraft that maneuvers in the gravitational field of an object of complex geometric shape using the asteroid 433 Eros and 951 Gaspra as examples. The choice of these asteroids is due to the presence of sufficient information about the gravitational fields of these bodies [10–12]. Besides, 433 Eros and 951 Gaspra are quite massive, and therefore it is impossible to ignore the uneven distribution of their gravitational field in space [12–14]. The authors used this information in [1, 15] to prove the correctness of the models used.

As a result of motion simulation, the authors developed an idea of using the iESP module for the controlled motion in the vicinity of the asteroid. Such modules are able to gain necessary thrust and exhaust velocity for the stable motion near the asteroid.

#### 2. Models of an irregular gravitational field

The chapter presents a model of the gravitational potential of asteroid 433 Eros and 951 Gaspra in terms of the applicability of the model in the problems of flight dynamics. It should be noted that the described model of motion does not require fundamental knowledge about the structure and composition of the object. The purpose of the analysis is to show that this method of describing the gravitational potential provides sufficient accuracy for subsequent flight design.

This work uses the asteroids 433 Eros and 951 Gaspra as examples cosmic bodies with irregular gravitational fields. The choices of these asteroids are explained by the shape of the asteroid, its mass and its orbit. According to [14], the physical properties and orbital characteristics asteroids are presented in Table 1.

Using the iESP Installed on the Space Station Moving in an Irregular Gravitational Field… DOI: http://dx.doi.org/10.5772/intechopen.85615

Figure 1. Asteroid Eros 433 as a superposition of two rotation mass points.

A number of mathematical methods can be used for deriving a model of an irregular gravitational field. This chapter suggests the model of gravitational potential based on the n-body problem. Authors developed the idea of superposition of single gravitate mass points potential. The problem is to determine the necessary number of mass points and to define their locations. It is considered that two gravity points suffice for the simulation of gravitational field. It should be noted that the model under consideration assume that the asteroid's density is distributed evenly throughout the body to simplify the calculations.

In the paper [15], authors compare the barycentrical form of gravitational potential and gravitational potential in spherical harmonic coefficients. It is proved that barycentric potential is accurate enough for the motion simulations.

Let M1, M<sup>2</sup> is masses of gravity points and r<sup>1</sup> ¼ x1; y1; z<sup>1</sup> , <sup>r</sup><sup>2</sup> <sup>¼</sup> <sup>x</sup>2, y2, z<sup>2</sup> are their vector positions (Figure 1). The corresponding form of the gravitational potential Ux, y, <sup>z</sup> for this case is taken from [16]:


Table 1.

Physical and orbital characteristics of the asteroids 433 Eros and 951 Gaspra.

modeling of spacecraft motion and the development of control schemes near asteroids and comets is possible only under the condition that those bodies gravitational field formalization task was solved with the prescribed accuracy. However, if we take into consideration cavities and voids in the object structure, the center of masses displacement, and the uneven distribution of density [5], it becomes diffi-

In addition to the high accuracy of the gravitational field model, the lightweight

The problem of finding the correct mathematical description of the gravitational fields of different shaped objects was addressed in a number of sources. For example, in the paper [6], the authors address the polygonal method of presenting the gravitational potential of asteroid 4769 Castalia as a formal model. A comparison of the proposed approach with the model of point attracting center takes place in the paper [7], where authors present a comparative analysis of the polygonal model and the model of point attracting center for the asteroid 216 Cleopatra. The paper [8] described and compared the gravitational potential presented in the form of series expanded into spherical, spheroidal, and ellipsoidal functions for Martian moons. In the paper [9], the authors address the position of equilibrium points for 23 different

The drawbacks of the approaches addressed are their cumbersomeness when using in the problems of spacecraft flight dynamics and the necessity to know in advance the physical properties of the objects—geometry and mass distribution. Modeling the gravitational field of objects whose properties and structure are not

This work analyzes the possibility of using ion electrospray propulsions to stabilize the orbit of a spacecraft that maneuvers in the gravitational field of an object of complex geometric shape using the asteroid 433 Eros and 951 Gaspra as examples. The choice of these asteroids is due to the presence of sufficient information about the gravitational fields of these bodies [10–12]. Besides, 433 Eros and 951 Gaspra are quite massive, and therefore it is impossible to ignore the uneven distribution of their gravitational field in space [12–14]. The authors used this information in

As a result of motion simulation, the authors developed an idea of using the

The chapter presents a model of the gravitational potential of asteroid 433 Eros

This work uses the asteroids 433 Eros and 951 Gaspra as examples cosmic bodies with irregular gravitational fields. The choices of these asteroids are explained by the shape of the asteroid, its mass and its orbit. According to [14], the physical properties and orbital characteristics asteroids are presented in Table 1.

iESP module for the controlled motion in the vicinity of the asteroid. Such modules are able to gain necessary thrust and exhaust velocity for the stable

and 951 Gaspra in terms of the applicability of the model in the problems of flight dynamics. It should be noted that the described model of motion does not require fundamental knowledge about the structure and composition of the object. The purpose of the analysis is to show that this method of describing the gravita-

tional potential provides sufficient accuracy for subsequent flight design.

motion modeling and the task of finding optimally sustainable control schemes are virtually non-solvable because of the overloaded model of gravitational potential. That is why the task is to find a balance between the accuracy of the object's

of the model plays a huge role in ballistic design. The task of the spacecraft

cult to solve the gravitational field formalization problem.

Electrospinning and Electrospraying - Techniques and Applications

potential appearance and the convergence property of the task.

asteroids in their polygonal models of gravitational fields.

known in advance within the models described is not possible.

[1, 15] to prove the correctness of the models used.

2. Models of an irregular gravitational field

motion near the asteroid.

90

Figure 2. Gravitational force lines of the Eros.

$$U\_{\mathbf{x},y,z} = G \cdot \sum\_{i=1}^{K=2} \frac{M\_i}{\sqrt{\left(\mathbf{x} - \mathbf{x}\_i\right)^2 + \left(y - y\_i\right)^2 + \left(z - z\_i\right)^2}} \tag{1}$$

$$\boxed{C(M\_1 + M\_2)}$$

$$
\rho = \sqrt{\frac{G(M\_1 + M\_2)}{d^3}} \tag{2}
$$

potential (1) in the inertial Cartesian three-dimensional coordinate system, which begins at the mass center Bs (Figure 3). The axis BsZ associates with the axis of

Using the iESP Installed on the Space Station Moving in an Irregular Gravitational Field…

• the asteroid and the spacecraft are moving in the plane XBsY, the asteroid

• the spacecraft has no impact on mass points motions (restricted circular three

rotates clockwise, and the spacecraft rotates counter clockwise;

• the Sun's gravity has impacted to the spacecraft and asteroid [17].

Vector form of the differential equations of the disturbed spacecraft's

<sup>3</sup> ð Þþ r � r<sup>i</sup> μSun

where P is controlling thrust vector; τ is propellant consumption per second; δ is Boolean-function of the engine operating condition (it can be 0 or 1); and mSV is the

From now on, a radius is in km, velocity is in kilometer per second, thrust is in

method (fourth-order accuracy). It is also noteworthy that all osculating parameters of orbit were obtained in the presumption that the asteroid's mass localizes in

We used the spacecraft's parameters, like to the missions Dawn and Rosetta [18], to simulate motion in these cases. The spacecraft's mass is 1200 kg and the exhaust velocity of the engine is 20 km/s. The initial commencing speed in every case was

dmSV

Newton, and angle is in radians. The integration scheme is the Runge-Kutta

Δ <sup>Δ</sup><sup>3</sup> � <sup>r</sup> r3 

þ P mSV

dt ¼ �δτ (4)

; (3)

We used the following assumptions to the simulations:

n i¼1

spacecraft mass, μSun is gravity parameter of Sun.

Mi ri

asteroid's rotation.

body problem);

d2 r dt<sup>2</sup> ¼ �<sup>G</sup> <sup>∑</sup>

DOI: http://dx.doi.org/10.5772/intechopen.85615

motion is [16]:

barycentre point.

Figure 3.

93

Scheme of the three body problem.

where G is the gravitational constant; r ¼ ð Þ x; y; z is vector of a spacecraft's position; ω is the angular velocity of the rotating around the barycentre; and d is the distance between the mass points. Hereafter, we call the potential (1) as the barycentric potential.

For example, in [15] we have analyzed the gravitational field of the asteroid 433 Eros and have calculated the exact mass values and the distance between the gravity points by trial and errors method. The following parameters of model <sup>M</sup><sup>1</sup> <sup>¼</sup> <sup>4</sup>:<sup>356</sup> � <sup>10</sup><sup>15</sup> kg, <sup>M</sup><sup>2</sup> <sup>¼</sup> <sup>2</sup>:<sup>334</sup> � <sup>10</sup><sup>15</sup> kg, <sup>d</sup> <sup>¼</sup> <sup>10</sup>:8 km, and <sup>ω</sup> <sup>¼</sup> <sup>5</sup>:<sup>6</sup> � <sup>10</sup>�<sup>4</sup> rad/s provide a minimum error in comparison with the gravitational potential described in the paper [11]. Figure 2 shows the corresponding graph of the gravitational potential force lines for the Eros.

#### 3. Motion simulation in an irregular gravitational field for an electric propulsion spacecraft

#### 3.1 Simulation a passive spacecraft's motion

As we have already mentioned, the gravitational potential of the object can be represented as a set of attracting point masses. We will address the gravitational

Using the iESP Installed on the Space Station Moving in an Irregular Gravitational Field… DOI: http://dx.doi.org/10.5772/intechopen.85615

potential (1) in the inertial Cartesian three-dimensional coordinate system, which begins at the mass center Bs (Figure 3). The axis BsZ associates with the axis of asteroid's rotation.

We used the following assumptions to the simulations:


Vector form of the differential equations of the disturbed spacecraft's motion is [16]:

$$\frac{d^2\mathbf{r}}{dt^2} = -G\sum\_{i=1}^n \frac{M\_i}{\mathbf{r}\_i^3} (\mathbf{r} - \mathbf{r}\_i) + \mu\_{\text{Sun}} \left(\frac{\Delta}{\Delta^3} - \frac{\mathbf{r}}{r^3}\right) + \frac{\mathbf{P}}{m\_{SV}};\tag{3}$$

$$\frac{dm\_{SV}}{dt} = -\delta\tau\tag{4}$$

where P is controlling thrust vector; τ is propellant consumption per second; δ is Boolean-function of the engine operating condition (it can be 0 or 1); and mSV is the spacecraft mass, μSun is gravity parameter of Sun.

From now on, a radius is in km, velocity is in kilometer per second, thrust is in Newton, and angle is in radians. The integration scheme is the Runge-Kutta method (fourth-order accuracy). It is also noteworthy that all osculating parameters of orbit were obtained in the presumption that the asteroid's mass localizes in barycentre point.

We used the spacecraft's parameters, like to the missions Dawn and Rosetta [18], to simulate motion in these cases. The spacecraft's mass is 1200 kg and the exhaust velocity of the engine is 20 km/s. The initial commencing speed in every case was

Figure 3. Scheme of the three body problem.

Ux, y, <sup>z</sup> ¼ G � ∑

barycentric potential.

Gravitational force lines of the Eros.

Figure 2.

potential force lines for the Eros.

propulsion spacecraft

92

3.1 Simulation a passive spacecraft's motion

K¼2 i¼1

Electrospinning and Electrospraying - Techniques and Applications

ω ¼

ð Þ x � xi

where G is the gravitational constant; r ¼ ð Þ x; y; z is vector of a spacecraft's position; ω is the angular velocity of the rotating around the barycentre; and d is the

<sup>M</sup><sup>1</sup> <sup>¼</sup> <sup>4</sup>:<sup>356</sup> � <sup>10</sup><sup>15</sup> kg, <sup>M</sup><sup>2</sup> <sup>¼</sup> <sup>2</sup>:<sup>334</sup> � <sup>10</sup><sup>15</sup> kg, <sup>d</sup> <sup>¼</sup> <sup>10</sup>:8 km, and <sup>ω</sup> <sup>¼</sup> <sup>5</sup>:<sup>6</sup> � <sup>10</sup>�<sup>4</sup> rad/s provide a minimum error in comparison with the gravitational potential described in the paper [11]. Figure 2 shows the corresponding graph of the gravitational

3. Motion simulation in an irregular gravitational field for an electric

As we have already mentioned, the gravitational potential of the object can be represented as a set of attracting point masses. We will address the gravitational

For example, in [15] we have analyzed the gravitational field of the asteroid 433 Eros and have calculated the exact mass values and the distance between the gravity

s

distance between the mass points. Hereafter, we call the potential (1) as the

points by trial and errors method. The following parameters of model

Mi ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi

� �<sup>2</sup> <sup>þ</sup> ð Þ <sup>z</sup> � zi

<sup>q</sup> (1)

2

(2)

<sup>2</sup> <sup>þ</sup> <sup>y</sup> � yi

ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi G Mð Þ <sup>1</sup> þ M<sup>2</sup> d3

chosen close to the circular velocity of the asteroid as the body with only one gravity point. The launch date is May 30, 2018. The authors developed the software for simulating spacecraft motion in irregular and regular gravitational fields [1].

To compare the impact of the distance from asteroid Eros on the spacecraft trajectory, we proposed to perform motion simulation for two orbit altitudes—50 km and 100 km. The same simulation to the asteroid Gaspra was performed for an orbit altitude of 200 km. Table 2 presents the initial conditions for the three cases.

Figures 4 and 5 illustrate the trajectories of the passive spacecraft motion for two orbit altitudes in the plane: 50 km and 100 km from asteroid Eros. According to the graphs, orbits are not stable; moreover, in the first case, the spacecraft hits the asteroid after 18.35 days.

#### 3.2 Simulation controlled spacecraft's motion: locally optimal controlled law

One of the problems of controlled spacecraft motion simulation is to find simple schemes to control the spacecraft that allow performing some simple maneuvers or stabilizing an orbit.


The primary requirement for these control schemes is the simplicity in operation. Consequently, it is suggested to use locally optimal actions based on osculating orbital elements. A spacecraft is assumed to move along the barycentric orbit, and corresponding osculating elements appertain to this orbit's plane. According to [17], application of the laws based on osculating orbital elements in this particular case allows obtaining a stable orbit for a spacecraft with an electric propulsion engine. It is suggested to use an angle η between the radius vector of the spacecraft r and the

Trajectory of passive spacecraft motion near the Eros in the plane XBsY (case Eros2) <sup>r</sup> <sup>¼</sup> ð Þ 0 100 0 <sup>T</sup>;

Using the iESP Installed on the Space Station Moving in an Irregular Gravitational Field…

Barycentric rectangular coordinate system—the Eros and the spacecraft appertain to the plane.

propulsive force vector P (Figure 6).

.

DOI: http://dx.doi.org/10.5772/intechopen.85615

Figure 5.

Figure 6.

95

<sup>V</sup> <sup>¼</sup> 0 2:<sup>1</sup> � <sup>10</sup>�<sup>3</sup> <sup>0</sup> <sup>T</sup>

#### Table 2.

Initial conditions for the three cases of simulation.

#### Figure 4.

Trajectory of passive spacecraft motion near the Eros in the plane XBsY (case Eros1) <sup>r</sup> <sup>¼</sup> ð Þ 0 50 0 <sup>T</sup>;<sup>V</sup> <sup>¼</sup> 0 2:<sup>98</sup> � <sup>10</sup>�<sup>3</sup> <sup>0</sup> <sup>T</sup> .

Using the iESP Installed on the Space Station Moving in an Irregular Gravitational Field… DOI: http://dx.doi.org/10.5772/intechopen.85615

#### Figure 5.

chosen close to the circular velocity of the asteroid as the body with only one gravity point. The launch date is May 30, 2018. The authors developed the software for simulating spacecraft motion in irregular and regular gravitational fields [1]. To compare the impact of the distance from asteroid Eros on the spacecraft trajectory, we proposed to perform motion simulation for two orbit altitudes—50 km and 100 km. The same simulation to the asteroid Gaspra was performed for an orbit altitude of 200 km. Table 2 presents the initial conditions for the three cases.

Electrospinning and Electrospraying - Techniques and Applications

Figures 4 and 5 illustrate the trajectories of the passive spacecraft motion for two orbit altitudes in the plane: 50 km and 100 km from asteroid Eros. According to the graphs, orbits are not stable; moreover, in the first case, the spacecraft hits the

3.2 Simulation controlled spacecraft's motion: locally optimal controlled law

Case r, km V, km/s Eros1 <sup>50</sup> 2.98� <sup>10</sup>�<sup>3</sup> Eros2 <sup>100</sup> 2.1� <sup>10</sup>�<sup>3</sup> Gaspra1 <sup>100</sup> 2.76� <sup>10</sup>�<sup>3</sup>

Trajectory of passive spacecraft motion near the Eros in the plane XBsY (case Eros1)

.

<sup>r</sup> <sup>¼</sup> ð Þ 0 50 0 <sup>T</sup>;<sup>V</sup> <sup>¼</sup> 0 2:<sup>98</sup> � <sup>10</sup>�<sup>3</sup> <sup>0</sup> <sup>T</sup>

One of the problems of controlled spacecraft motion simulation is to find simple schemes to control the spacecraft that allow performing some simple maneuvers or

asteroid after 18.35 days.

stabilizing an orbit.

Initial conditions for the three cases of simulation.

Table 2.

Figure 4.

94

Trajectory of passive spacecraft motion near the Eros in the plane XBsY (case Eros2) <sup>r</sup> <sup>¼</sup> ð Þ 0 100 0 <sup>T</sup>; <sup>V</sup> <sup>¼</sup> 0 2:<sup>1</sup> � <sup>10</sup>�<sup>3</sup> <sup>0</sup> <sup>T</sup> .

The primary requirement for these control schemes is the simplicity in operation. Consequently, it is suggested to use locally optimal actions based on osculating orbital elements. A spacecraft is assumed to move along the barycentric orbit, and corresponding osculating elements appertain to this orbit's plane. According to [17], application of the laws based on osculating orbital elements in this particular case allows obtaining a stable orbit for a spacecraft with an electric propulsion engine. It is suggested to use an angle η between the radius vector of the spacecraft r and the propulsive force vector P (Figure 6).

Figure 6. Barycentric rectangular coordinate system—the Eros and the spacecraft appertain to the plane.

The constant semi-major axis law is considered [17] as the control law:

$$\text{tg}\eta = -\frac{e\sin\theta}{1+e\cos\theta} \tag{5}$$

where ϑ is true anomaly and e is eccentricity of the barycentric orbit. The equations of the control thrust vector are:

$$P\_{\mathbf{x}} = \frac{r\_{\mathbf{x}}}{\sqrt{r\_{\mathbf{x}}^2 + r\_{\mathbf{y}}^2}} \cos \eta - \frac{r\_{\mathbf{y}}}{\sqrt{r\_{\mathbf{x}}^2 + r\_{\mathbf{y}}^2}} \sin \eta \tag{6}$$

$$P\_{\mathcal{Y}} = \frac{r\_{\mathcal{Y}}}{\sqrt{r\_{\mathbf{x}}^2 + r\_{\mathcal{Y}}^2}} \cos \eta + \frac{r\_{\mathbf{x}}}{\sqrt{r\_{\mathbf{x}}^2 + r\_{\mathcal{Y}}^2}} \sin \eta \tag{7}$$

$$P\_x = \mathbf{0} \tag{8}$$

Figure 9.

97

Figure 8.

(b) eccentricity.

and (c) longitude of the ascending node.

Graphs of changes in the parameters of the trajectory (case Eros1). (a) Focal parameter, (b) inclination,

Graphs of changes in the parameters of the trajectory (case Eros1). (a) The angle of the true anomaly and

Using the iESP Installed on the Space Station Moving in an Irregular Gravitational Field…

DOI: http://dx.doi.org/10.5772/intechopen.85615

The simulation parameters were determinated earlier. Additionally, the specific impulse of the engine module is IsP1 = 1000 s, IsP2 = 1500 s, and IsP3 = 2000 s. The trust values are various for the particular altitude. The particular values were obtained by the direct-search method.

The interpolated values of thrust levels for the orbit's stabilization control scheme (16) for IsP1 = 1000 s, IsP2 = 1500 s, and IsP3 = 2000 s are represented in Figure 7.

Figures 8 and 9 show graphs of changes in orbit parameters in case Eros1 and the engines with IsP1 = 1500 s.

Figure 10 shows the trajectory of spacecraft's motion in the OXY for 50 km Eros' orbit (case Eros1). The characteristic of thrust for the orbit altitude in 50 km and for the orbit altitude of 100 km are shown in Table 3.

Figure 11 shows trajectory of spacecraft's motion in the OXY for 100 km Eros' orbit (case Eros2).

Consider the trajectory of motion for the case of asteroid Gaspra, obtained by using the locally optimal control law—the constancy of the distance of the semi major axis (Figure 12), as well as graphs of changes in the barycentric coordinates

Figure 7. Dependency of the thrust level to the barycentre distance and the specific impulse of propulsion system.

Using the iESP Installed on the Space Station Moving in an Irregular Gravitational Field… DOI: http://dx.doi.org/10.5772/intechopen.85615

#### Figure 8.

The constant semi-major axis law is considered [17] as the control law:

where ϑ is true anomaly and e is eccentricity of the barycentric orbit.

The equations of the control thrust vector are:

Electrospinning and Electrospraying - Techniques and Applications

obtained by the direct-search method.

the orbit altitude of 100 km are shown in Table 3.

the engines with IsP1 = 1500 s.

Figure 7.

Figure 7.

96

orbit (case Eros2).

Px <sup>¼</sup> rx ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi rx <sup>2</sup> þ ry

Py <sup>¼</sup> ry ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi rx <sup>2</sup> þ ry <sup>2</sup> <sup>p</sup> cos <sup>η</sup> <sup>þ</sup>

tg<sup>η</sup> ¼ � <sup>e</sup>sin <sup>ϑ</sup>

<sup>2</sup> <sup>p</sup> cos <sup>η</sup> � ry ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi

The simulation parameters were determinated earlier. Additionally, the specific impulse of the engine module is IsP1 = 1000 s, IsP2 = 1500 s, and IsP3 = 2000 s. The trust values are various for the particular altitude. The particular values were

The interpolated values of thrust levels for the orbit's stabilization control scheme (16) for IsP1 = 1000 s, IsP2 = 1500 s, and IsP3 = 2000 s are represented in

Figures 8 and 9 show graphs of changes in orbit parameters in case Eros1 and

Figure 10 shows the trajectory of spacecraft's motion in the OXY for 50 km Eros' orbit (case Eros1). The characteristic of thrust for the orbit altitude in 50 km and for

Figure 11 shows trajectory of spacecraft's motion in the OXY for 100 km Eros'

Consider the trajectory of motion for the case of asteroid Gaspra, obtained by using the locally optimal control law—the constancy of the distance of the semi major axis (Figure 12), as well as graphs of changes in the barycentric coordinates

Dependency of the thrust level to the barycentre distance and the specific impulse of propulsion system.

rx <sup>2</sup> þ ry

rx ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi rx <sup>2</sup> þ ry

<sup>1</sup> <sup>þ</sup> <sup>e</sup> cos <sup>ϑ</sup> (5)

<sup>2</sup> <sup>p</sup> sin <sup>η</sup> (6)

<sup>2</sup> <sup>p</sup> sin <sup>η</sup> (7)

Pz ¼ 0 (8)

Graphs of changes in the parameters of the trajectory (case Eros1). (a) The angle of the true anomaly and (b) eccentricity.

#### Figure 9.

Graphs of changes in the parameters of the trajectory (case Eros1). (a) Focal parameter, (b) inclination, and (c) longitude of the ascending node.

#### Figure 10.

Trajectory of spacecraft's motion near the Eros stabilized by the constant semi-major axis law <sup>r</sup> <sup>¼</sup> ð Þ 0 50 0 <sup>T</sup>; <sup>V</sup> <sup>¼</sup> 0 2:<sup>98</sup> � <sup>10</sup>�<sup>3</sup> <sup>0</sup> <sup>T</sup> , <sup>P</sup> <sup>¼</sup> <sup>6</sup>:<sup>6</sup> � <sup>10</sup>�<sup>5</sup> N (case Eros1).


Figure 11.

Figure 12.

99

The trajectory of the spacecraft for asteroid Gaspra (case Gaspra1).

<sup>r</sup> <sup>¼</sup> ð Þ 0 100 0 <sup>T</sup>; <sup>V</sup> <sup>¼</sup> 0 2:<sup>1</sup> � <sup>10</sup>�<sup>3</sup> <sup>0</sup> <sup>T</sup>

DOI: http://dx.doi.org/10.5772/intechopen.85615

Trajectory of spacecraft's motion near the Eros stabilized by the constant semi-major axis law

Using the iESP Installed on the Space Station Moving in an Irregular Gravitational Field…

, <sup>P</sup> <sup>¼</sup> <sup>8</sup> � <sup>10</sup>�<sup>6</sup>N (case Eros2).

#### Table 3.

Characteristics of thrust and exhaust velocity.

and velocities of the spacecraft (Figures 13 and 14) and graphs of changes in the orbit parameters (Figures 15 and 16).

#### 4. Ion electrospray thruster assembly for spacecraft maneuvering in vicinity of asteroid

Ion electrospray engine (iESP) is a micro-thruster that is designed initially for CubeSats technology. Besides, such engines can be used for motion control systems of small spacecraft as these engines have a sufficient duration of operation and low consumption of the working fluid. It is a type of low thrust electric propulsion rocket engine that uses electrostatic acceleration of charged liquid droplets for propulsion. The liquid used for this application tends to be a low-volatility ionic liquid. The most amenable propellants for electrostatic thrusters have proven to be

Using the iESP Installed on the Space Station Moving in an Irregular Gravitational Field… DOI: http://dx.doi.org/10.5772/intechopen.85615

Figure 11.

Trajectory of spacecraft's motion near the Eros stabilized by the constant semi-major axis law <sup>r</sup> <sup>¼</sup> ð Þ 0 100 0 <sup>T</sup>; <sup>V</sup> <sup>¼</sup> 0 2:<sup>1</sup> � <sup>10</sup>�<sup>3</sup> <sup>0</sup> <sup>T</sup> , <sup>P</sup> <sup>¼</sup> <sup>8</sup> � <sup>10</sup>�<sup>6</sup>N (case Eros2).

Figure 12. The trajectory of the spacecraft for asteroid Gaspra (case Gaspra1).

and velocities of the spacecraft (Figures 13 and 14) and graphs of changes in the

Trajectory of spacecraft's motion near the Eros stabilized by the constant semi-major axis law

Electrospinning and Electrospraying - Techniques and Applications

, <sup>P</sup> <sup>¼</sup> <sup>6</sup>:<sup>6</sup> � <sup>10</sup>�<sup>5</sup>

Case r, km P, N c, km/s Eros1 <sup>50</sup> 6.6 � <sup>10</sup>�<sup>5</sup> <sup>15</sup> Eros2 <sup>100</sup> <sup>8</sup> � <sup>10</sup>�<sup>6</sup> <sup>15</sup> Gaspra1 <sup>100</sup> 2.33 � <sup>10</sup>�<sup>5</sup> <sup>20</sup>

N (case Eros1).

4. Ion electrospray thruster assembly for spacecraft maneuvering in

Ion electrospray engine (iESP) is a micro-thruster that is designed initially for CubeSats technology. Besides, such engines can be used for motion control systems of small spacecraft as these engines have a sufficient duration of operation and low consumption of the working fluid. It is a type of low thrust electric propulsion rocket engine that uses electrostatic acceleration of charged liquid droplets for propulsion. The liquid used for this application tends to be a low-volatility ionic liquid. The most amenable propellants for electrostatic thrusters have proven to be

orbit parameters (Figures 15 and 16).

Characteristics of thrust and exhaust velocity.

<sup>r</sup> <sup>¼</sup> ð Þ 0 50 0 <sup>T</sup>; <sup>V</sup> <sup>¼</sup> 0 2:<sup>98</sup> � <sup>10</sup>�<sup>3</sup> <sup>0</sup> <sup>T</sup>

vicinity of asteroid

Figure 10.

Table 3.

98

Graphs of changes in the parameters of the trajectory (case Gaspra1). (a) X coordinate, (b) the Y coordinates, and (c) Z coordinates.

Figure 14.

Figure 15.

101

the true anomaly.

(c) Vz velocity.

Graphs of changes in the parameters of the trajectory (case Gaspra1). (a) Vx velocity, (b) Vy velocity, and

Using the iESP Installed on the Space Station Moving in an Irregular Gravitational Field…

DOI: http://dx.doi.org/10.5772/intechopen.85615

Graphs of changes in the parameters of the trajectory (case Gaspra1). (a) The eccentricity and (b) the angle of

cesium, mercury, argon, krypton, and most commonly xenon, and many possible sources of such ions of the requisite efficiency, reliability, and uniformity have been conceived and developed [19].

The typical design appearances of an electrospray thruster are shown Figures 17 and 18.

Like other ion thrusters, the main benefits of iESP include high efficiency, thrust density, and specific impulse; however, it has shallow total thrust, on the order of micro-Newton. It provides excellent attitude control or dynamic acceleration of small spacecraft over long periods.

The spacecraft's motion simulation in asteroid's vicinity identifies that engine specification for the stabilization trajectories is close to the Ion electrospray thrusters' modules in the context of the thrust level and IsP. Therefore, we propose to use them not only as executive bodies of the control system, but also to stabilize the orbital motion of the spacecraft, which is unstable due to the disturbing action of an irregular gravitational field. The appearance of the control program identifies the number of demands for the electrospray engines module that is installed on the spacecraft. It can be used for the particular configuration of the power plant's design.

Using the iESP Installed on the Space Station Moving in an Irregular Gravitational Field… DOI: http://dx.doi.org/10.5772/intechopen.85615

Figure 14.

cesium, mercury, argon, krypton, and most commonly xenon, and many possible sources of such ions of the requisite efficiency, reliability, and uniformity have been

Graphs of changes in the parameters of the trajectory (case Gaspra1). (a) X coordinate, (b) the Y coordinates,

Electrospinning and Electrospraying - Techniques and Applications

The typical design appearances of an electrospray thruster are shown Figures 17

Like other ion thrusters, the main benefits of iESP include high efficiency, thrust density, and specific impulse; however, it has shallow total thrust, on the order of micro-Newton. It provides excellent attitude control or dynamic acceleration of

The spacecraft's motion simulation in asteroid's vicinity identifies that engine specification for the stabilization trajectories is close to the Ion electrospray thrusters' modules in the context of the thrust level and IsP. Therefore, we propose to use them not only as executive bodies of the control system, but also to stabilize the orbital motion of the spacecraft, which is unstable due to the disturbing action of an irregular gravitational field. The appearance of the control program identifies the number of demands for the electrospray engines module that is installed on the spacecraft. It can

be used for the particular configuration of the power plant's design.

conceived and developed [19].

small spacecraft over long periods.

and 18.

100

Figure 13.

and (c) Z coordinates.

Graphs of changes in the parameters of the trajectory (case Gaspra1). (a) Vx velocity, (b) Vy velocity, and (c) Vz velocity.

Figure 15.

Graphs of changes in the parameters of the trajectory (case Gaspra1). (a) The eccentricity and (b) the angle of the true anomaly.

Figures 19–21 show diagrams of the control law for the cases Eros1, Eros2, and Gaspra1 (control programs). It can be seen from the graphs that small changes in the direction of thrust of the engine (within 10°), according to the selected control law, allows making the flight orbits stable. Such control rules can be used to

Using the iESP Installed on the Space Station Moving in an Irregular Gravitational Field…

DOI: http://dx.doi.org/10.5772/intechopen.85615

maneuver near an asteroid with an uneven gravitational field.

The control program for the constant semi-major axis (50 km) (case Eros1).

Figure 18. Electric engine.

Figure 19.

103

Graphs of changes in the parameters of the trajectory (case Gaspra1). (a) Focal parameter, (b) inclination, and (c) longitude of the ascending node.

Figure 17. Electrospray thruster.

Using the iESP Installed on the Space Station Moving in an Irregular Gravitational Field… DOI: http://dx.doi.org/10.5772/intechopen.85615

Figure 16.

Figure 17. Electrospray thruster.

102

and (c) longitude of the ascending node.

Graphs of changes in the parameters of the trajectory (case Gaspra1). (a) Focal parameter, (b) inclination,

Electrospinning and Electrospraying - Techniques and Applications

Figures 19–21 show diagrams of the control law for the cases Eros1, Eros2, and Gaspra1 (control programs). It can be seen from the graphs that small changes in the direction of thrust of the engine (within 10°), according to the selected control law, allows making the flight orbits stable. Such control rules can be used to maneuver near an asteroid with an uneven gravitational field.

Thus, iESP modules can be successfully used not only for the control angular

The simulation results of the orbital stabilization for other engines (for other specific impulse and thrust values) and orbit altitudes were not represented in the chapter; however, the obtained values were used for interpolation lines (Figure 6). Thrust levels were variable parameters that depend on the orbit altitude and the initial commencing speed. Figure 22 shows the range of settings of electric propulsion systems suitable for use as an engine for maneuvering or stabilizing

This chapter discusses the use of electrospray engines to stabilize near-asteroid

The obtained results are used to simulate the passive and controlled motion of a spacecraft as an n-body problem. It is established that passive motion is unstable. The authors proposed to use the known locally optimal control law for orbit stabilization. A constant semi-axis control law of thrust was used to model the motion of three orbits (50, 100, and 200 km) near two asteroids (Eros and Gaspra) to stabilize. The levels of thrust and specific impulse and their dependence on the orbit

The simulation results show that the calculated thrust and specific impulse (or exhaust velocity) levels are within the range of ion motor characteristics. However, it is necessary to take into account the received control programs and the real and mass of the spacecraft. Therefore, under all these assumptions, it is possible to use

nonspherical. Mathematical models of the asteroid's gravitational field and controlled motion of a spacecraft with an electric motor in an uneven gravitational field

orbits. Presents two of the asteroids Eros and Gaspra have substantially

height, initial velocity, and asteroid parameters were determined.

the ion electrospray module for motion near asteroids.

motion, but also for the movement in the vicinity of an asteroid in different

Using the iESP Installed on the Space Station Moving in an Irregular Gravitational Field…

DOI: http://dx.doi.org/10.5772/intechopen.85615

Electric engine thrust/IsP distribution for suitable electric propulsion systems.

research missions.

Figure 22.

near-asteroid orbits.

5. Conclusions

are developed.

105

Figure 20. The control program for the constant semi-major axis (100 km) (case Eros2).

Figure 21. The control program for the constant semi-major axis (100 km) (case Gaspra1).

Using the iESP Installed on the Space Station Moving in an Irregular Gravitational Field… DOI: http://dx.doi.org/10.5772/intechopen.85615

Figure 22. Electric engine thrust/IsP distribution for suitable electric propulsion systems.

Thus, iESP modules can be successfully used not only for the control angular motion, but also for the movement in the vicinity of an asteroid in different research missions.

The simulation results of the orbital stabilization for other engines (for other specific impulse and thrust values) and orbit altitudes were not represented in the chapter; however, the obtained values were used for interpolation lines (Figure 6). Thrust levels were variable parameters that depend on the orbit altitude and the initial commencing speed. Figure 22 shows the range of settings of electric propulsion systems suitable for use as an engine for maneuvering or stabilizing near-asteroid orbits.

#### 5. Conclusions

Figure 20.

Figure 21.

The control program for the constant semi-major axis (100 km) (case Eros2).

Electrospinning and Electrospraying - Techniques and Applications

The control program for the constant semi-major axis (100 km) (case Gaspra1).

This chapter discusses the use of electrospray engines to stabilize near-asteroid orbits. Presents two of the asteroids Eros and Gaspra have substantially nonspherical. Mathematical models of the asteroid's gravitational field and controlled motion of a spacecraft with an electric motor in an uneven gravitational field are developed.

The obtained results are used to simulate the passive and controlled motion of a spacecraft as an n-body problem. It is established that passive motion is unstable. The authors proposed to use the known locally optimal control law for orbit stabilization. A constant semi-axis control law of thrust was used to model the motion of three orbits (50, 100, and 200 km) near two asteroids (Eros and Gaspra) to stabilize. The levels of thrust and specific impulse and their dependence on the orbit height, initial velocity, and asteroid parameters were determined.

The simulation results show that the calculated thrust and specific impulse (or exhaust velocity) levels are within the range of ion motor characteristics. However, it is necessary to take into account the received control programs and the real and mass of the spacecraft. Therefore, under all these assumptions, it is possible to use the ion electrospray module for motion near asteroids.

The simulation results show that the calculated thrust and exhaust velocity levels are too low for the spacecraft's main engines. Thus, to guarantee the design characteristics, it is necessary to use an additional module iESP.

References

33-6440

1987

[1] Shornikov A, Starinova O.

sustainer engine installed on a

Effectiveness analyses of an electrospray

DOI: http://dx.doi.org/10.5772/intechopen.85615

harmonic expansion from the near Doppler track data. Geophysical Research Letters. 2002;29(8)

[12] Miller JK et al. Determination of shape, gravity, and rotational state of asteroid 433 Eros. Icarus. 2002;155(1):

[13] Moore C. Technology Development for NASA's Asteroid Redirect Mission, IAC-14-D2.8-A5.4.1. Available from: https://www.nasa.gov/sites/default/iles/ iles/IAC-14-D2\_8-A5\_4\_1-Moore.pdf

[14] Asteroids internet base. Available from: http://space.frieger.com/asteroids/

International Conference on Recent Advances in Space Technologies (RAST); 16–19 June 2015; Istanbul,

[16] Szebehely V. Theory of Orbits: The Restricted Problem of Three Bodies. New Haven, CT: Yale University; 1967.

[17] Lebedev V. The Calculation of the Motion of a Spacecraft with Low Thrust. Moscow: Computation Centre of the Russian Academy of Sciences; 1968.

[18] Scheeres D. The orbital dynamics environment of 433 Eros. Ann Arbor.

[19] Sheth V. Spacecraft electric propulsion—A review. International Journal of Research in Aeronautical and Mechanical Engineering. 2014;43-55.

Turkey. 2015. pp. 771-776

pp. 10-25

pp. 4-10

2002. 1001

ISSN: 2321-3051

[15] Shornikov A, Starinova O. Simulation of controlled motion in an irregular gravitational field for an electric propulsion spacecraft. In: Proceedings of the IEEE 7th

3-17

Using the iESP Installed on the Space Station Moving in an Irregular Gravitational Field…

spacecraft maneuvering in vicinity of an asteroid. Procedia Engineering. 2017

[2] Chapman CR, Morrison D. On the Earth by asteroids and comet: Assessing the hazard. Nature. 1994;367:6458,

[3] Ross SD. Near-Earth asteroid mining space. Use of near-Earth asteroids as platforms for future space bases; 2001

[4] Moore S. Technology development

[5] Britt DT et al. Asteroid density, porosity, and structure. In: Asteroids III.

[6] Geissler P, Petit J-M, Durda D, Greenberg R, Bottke W, Nolan M, et al.

[7] Ren Y, Shan J. On tethered sample and mooring systems near irregular asteroids. Advances in Space Research.

comparison of spherical, spheroidal and ellipsoidal harmonic gravitational field models for small non-spherical bodies: Examples for the Martian moons. Journal of Geodesy. 2015;89(2):159-177

[9] Wang X, Jiang Y, Gong S. Analysis of the potential field and equilibrium points of irregular-shaped minor celestial bodies. Astrophysics and Space

[10] Michel P, Farinella P, Froeschlé C. The orbital evolution of the asteroid Eros and implications for collision with the Earth. Nature. 1996;380(6576):689

[11] Garmier R et al. Modeling of the Eros gravity field as is ellipsoidal

107

Icarus. 1996;120:140

2014;54(8):1608-1618

[8] Hu X, Jekeli C. A numerical

Science. 2014;353(1):105-121

for NASA's asteroid redirect

### Acknowledgements

The authors state that part of the chapter was taken from our previously published article (Andrey Shornikov, Irina Gorbunova, Olga Starinova "Stabilized Trajectories of a Spacecraft in Inhomogeneous Gravitational Fields," AIP Publishing, 2018), and that we have the copyright to re-use it. The reported study was funded by Ministry of Education and Science of the Russian Federation according to the research project No. AAAA-A17-117031050032-9 (9.5453.2017).

#### Author details

Olga Starinova<sup>1</sup> , Andrey Shornikov<sup>1</sup> and Elizaveta Nikolaeva<sup>2</sup> \*

1 Department of Space Engineering, Samara National Research University, Samara, Russia

2 Interuniversity Department of Space Research, Samara National Research University, Samara, Russia

\*Address all correspondence to: nikolaevalizaveta@mail.ru

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Using the iESP Installed on the Space Station Moving in an Irregular Gravitational Field… DOI: http://dx.doi.org/10.5772/intechopen.85615

#### References

The simulation results show that the calculated thrust and exhaust velocity levels are too low for the spacecraft's main engines. Thus, to guarantee the design charac-

The authors state that part of the chapter was taken from our previously published article (Andrey Shornikov, Irina Gorbunova, Olga Starinova "Stabilized Trajectories of a Spacecraft in Inhomogeneous Gravitational Fields," AIP Publishing, 2018), and that we have the copyright to re-use it. The reported study was funded by Ministry of Education and Science of the Russian Federation according to

, Andrey Shornikov<sup>1</sup> and Elizaveta Nikolaeva<sup>2</sup>

2 Interuniversity Department of Space Research, Samara National Research

\*Address all correspondence to: nikolaevalizaveta@mail.ru

1 Department of Space Engineering, Samara National Research University, Samara,

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*

the research project No. AAAA-A17-117031050032-9 (9.5453.2017).

teristics, it is necessary to use an additional module iESP.

Electrospinning and Electrospraying - Techniques and Applications

Acknowledgements

Author details

Olga Starinova<sup>1</sup>

University, Samara, Russia

provided the original work is properly cited.

Russia

106

[1] Shornikov A, Starinova O. Effectiveness analyses of an electrospray sustainer engine installed on a spacecraft maneuvering in vicinity of an asteroid. Procedia Engineering. 2017

[2] Chapman CR, Morrison D. On the Earth by asteroids and comet: Assessing the hazard. Nature. 1994;367:6458, 33-6440

[3] Ross SD. Near-Earth asteroid mining space. Use of near-Earth asteroids as platforms for future space bases; 2001

[4] Moore S. Technology development for NASA's asteroid redirect

[5] Britt DT et al. Asteroid density, porosity, and structure. In: Asteroids III. 1987

[6] Geissler P, Petit J-M, Durda D, Greenberg R, Bottke W, Nolan M, et al. Icarus. 1996;120:140

[7] Ren Y, Shan J. On tethered sample and mooring systems near irregular asteroids. Advances in Space Research. 2014;54(8):1608-1618

[8] Hu X, Jekeli C. A numerical comparison of spherical, spheroidal and ellipsoidal harmonic gravitational field models for small non-spherical bodies: Examples for the Martian moons. Journal of Geodesy. 2015;89(2):159-177

[9] Wang X, Jiang Y, Gong S. Analysis of the potential field and equilibrium points of irregular-shaped minor celestial bodies. Astrophysics and Space Science. 2014;353(1):105-121

[10] Michel P, Farinella P, Froeschlé C. The orbital evolution of the asteroid Eros and implications for collision with the Earth. Nature. 1996;380(6576):689

[11] Garmier R et al. Modeling of the Eros gravity field as is ellipsoidal

harmonic expansion from the near Doppler track data. Geophysical Research Letters. 2002;29(8)

[12] Miller JK et al. Determination of shape, gravity, and rotational state of asteroid 433 Eros. Icarus. 2002;155(1): 3-17

[13] Moore C. Technology Development for NASA's Asteroid Redirect Mission, IAC-14-D2.8-A5.4.1. Available from: https://www.nasa.gov/sites/default/iles/ iles/IAC-14-D2\_8-A5\_4\_1-Moore.pdf

[14] Asteroids internet base. Available from: http://space.frieger.com/asteroids/

[15] Shornikov A, Starinova O. Simulation of controlled motion in an irregular gravitational field for an electric propulsion spacecraft. In: Proceedings of the IEEE 7th International Conference on Recent Advances in Space Technologies (RAST); 16–19 June 2015; Istanbul, Turkey. 2015. pp. 771-776

[16] Szebehely V. Theory of Orbits: The Restricted Problem of Three Bodies. New Haven, CT: Yale University; 1967. pp. 10-25

[17] Lebedev V. The Calculation of the Motion of a Spacecraft with Low Thrust. Moscow: Computation Centre of the Russian Academy of Sciences; 1968. pp. 4-10

[18] Scheeres D. The orbital dynamics environment of 433 Eros. Ann Arbor. 2002. 1001

[19] Sheth V. Spacecraft electric propulsion—A review. International Journal of Research in Aeronautical and Mechanical Engineering. 2014;43-55. ISSN: 2321-3051

### *Edited by Sajjad Haider and Adnan Haider*

This book focuses on the recent advancements in the process parameters, research, and applications of electrospinning and electrospraying. The first chapter introduces the techniques and the effect of the parameters on the morphology of the nanofiber and nanoparticles and then the subsequent chapters focus on the applications of these techniques in different areas. This book will attract a broad audience including postgraduate students and industrial and academic investigators in sciences and engineering who wish to enhance their understanding of the emerging technologies and use this book as reference.

Published in London, UK © 2019 IntechOpen © Holcy / iStock

Electrospinning and Electrospraying - Techniques and Applications

Electrospinning and

Electrospraying

Techniques and Applications

*Edited by Sajjad Haider and Adnan Haider*