**1. Introduction**

Nowadays, the global increase in the number of people with chronic diseases as "cancer, diabetes, etc." have affected the health and quality of life of many citizens around the world. For example, cancer is considered a public health problem because of its high incidence and mortality. The World Health Organization (WHO) estimates 27 million cases of cancer and 17 million deaths disease for the year 2030 [1]. Therefore, study on cancer treatment has attracted many scientists. Among therapies, cancer chemotherapy is widely used despite its disadvantages. Chemotherapy usually causes serious side effects because of the low selectivity of anti-cancer drugs, which affects not only cancer cells but also normal cells [2]. Thus, increasing attention is being paid to targeted drug delivery systems, which have been used to increase the efficiency of drug delivery to specific tissues and to decrease the associated side effects.

The most efficient solution is to use nanoparticles embedded in the hydrogel; this innovative-targeted drug delivery strategy involves coupling the drug to magnetic nanoparticles (NPs) that can be guided to the target using external magnetic fields [3]. Once they reach the target, the nanoparticles release the drugs under the influence of an alternating magnetic field [4]. Nanoparticle (NP) targeting has shown great potential for cancer drug delivery applications over the past decade. From nanoparticle targeting, magneto-particle have been widely studied because of their ability to target when an external magnetic field is applied [5].

An increasing population causes serious environmental pollution, waste production is also increasing and major proportion of by-products generated by contemporary food remains underused which may often contain precious substances. The crucial problem confronting by industries and society in food processing is the elimination of food waste. Chitin is an important natural resource and the world's annual production of it is approximately 1010–1012 tons [6]. This latter is principally produced by mollusks, arthropods (crustaceans and insects) and fungi [7]. However, chitin and its derivatives have a high economic impact due to their numerous applications in the pharmaceutical [8], food [9, 10], cosmetics [11], textile [12], wastewater treatment and agricultural sectors [13].

In the past few decades, drug delivery systems (DDS) have been of great interest and resulted in many efforts to realize the effectiveness and targeted drug delivery tendency as well as to reduce the associated side effects [14]. However, DDS provide several advantages as compared to conventional dosages in terms of improved efficacy, reduced toxicity, improved patient compliance, and convenience [15]. Thus, the carriers used for drug release are generally biodegradable polymers which are extensively used for designing the control drug delivery systems [16].

On the other hand, with the rapid development of technology much attention has been given to use biopolymer based hydrogels in many applications including pharmaceuticals [17, 18], cosmetics [19], agriculture [20] and biotechnology [21, 22]. However, porous biomaterials fabricated from natural polymers "chitosan" were given significant attention for years. Chitosan is a unique natural cationic biopolymer produced by N-deacetylation of chitin and is the second most abundant natural polymer after cellulose [23]. Chitosan has been widely used in the biomedical field due to its superior properties including good biodegradability [24], biocompatibility [24], low toxicity [25, 26], mucoadhesive properties [27], antibacterial activity [28] and low cost [24, 29]. Chitosan is an excellent candidate for different applications particularly it has been employed in various FDA (Food and Drug Administration) approved biomedical applications. The -NH2 group of the (CS) chains is a pH-sensitive polymer with pKa around 6.5 due to variation of charge density at the pH range of 6–6.5, which is useful for wide range of pharmaceuticals applications. The pH value of the soluble-insoluble transition in the range 6–6.5 [30]. At pH levels beneath the pKa, high charge density of chitosan results in polyelectrolyte formation, in contrast at neutral pH, the low charge density of chitosan eases the intracellular release of biomolecules and contributes to its low cytotoxicity [31]. Chitosan has increasingly been used in the pharmaceutical field as it is one of the excellent choices for the Schiff's base linkages to form an injectable hydrogel due to the nature of abundant amino groups on its backbone. Hydrogels from chitosan

**5**

**Figure 1.**

*A Novel Drug Delivery System Based on Nanoparticles of Magnetite Fe3O4 Embedded in an Auto…*

are usually prepared through physical interchain interaction or chemical reaction of the free amine groups with crosslinker agents (e.g. glutaraldehyde, glyoxal [32]). The disadvantage of these crosslinking agents, especially glutaraldehyde [33], benzaldehyde [34] and glyoxal is their toxicity to human tissues even at small traces [35], which has limited the use of chitosan hydrogels as scaffolds for drug delivery. However, this paper discusses the recent trends in drug delivery systems (DDS) applications using macroscopic hydrogels. Hydrogel has received extensive attention due to its interconnected cross-linked porous hydrophilic polymer networks which can absorb large amounts of water or biological fluids. Additionally, hydrogels can be divided into three categories according to their size: macroscopic gels, nanogels (<200 nm), and microgels (0.5–10 μm). Hydrogels are promising, fashionable, intelligent and "smart" drug delivery vehicles that meet specific requirements for targeting drugs to specific sites and controlling drug release. The hydrogel-based drug carrier loaded with 5-fluorouracil (5-FU) drug for an up to 36 days sustained

Hydrogels are trendy, promising, intelligent and 'smart' drug delivery vehicles have become a great search field for targeting drugs to the specific sites and controlling drug release. Among several hardware platforms, ferrogels (FG) have a high potential for use in drug delivery. Ferrogels (FG) are consisting mainly of a polymer matrix embedded with magnetic micro and nano-particles (Fe3O4) [37–39]. Upon the application of an external magnetic field, the polymer matrix of the ferrogel can deform due to the magnetic force generated by the embedded magnetic particles, which would allow actuation and magnetically driven drug release on demand. The main advantage of ferrogels is that a larger quantity of drug can be loaded, com-

Ferrogel (FG) are typically prepared by incorporating magnetic particles into hydrogels [40]. Magnetic nanoparticles (Fe3O4) shown in **Figure 1**, have attracted much attention in the last few years as carriers for drug delivery systems. The potential use of nanoparticles as drug carriers has been presented in recent years as a major challenge, as nanoparticles have been designed to improve pharmacological and therapeutic effects in terms of reducing their toxic side effects. Besides, magnetite (Fe3O4) is considered as an important type of magnetic material with cubic inverse spinel structure. This property makes it very interesting because of its wide field of use, including magnetic recording, ferrofluid [41], catalyst [42] and some biomedical applications like magnetic resonance imaging (MRI) [43], bio separation [44], in addition to drug delivery system and therapeutic hyperthermia as well, to treat cancer and tumors [45]. Several methods have been developed recently

pared to that transported by simple magnetic dispersion nanoparticles.

*Model of crystal structure of magnetite (Fe3O4) and spherical Fe3O4 nanoparticles.*

*DOI: http://dx.doi.org/10.5772/intechopen.94873*

delivery has been studied by Xueyun Chen et al. [36].

#### *A Novel Drug Delivery System Based on Nanoparticles of Magnetite Fe3O4 Embedded in an Auto… DOI: http://dx.doi.org/10.5772/intechopen.94873*

are usually prepared through physical interchain interaction or chemical reaction of the free amine groups with crosslinker agents (e.g. glutaraldehyde, glyoxal [32]). The disadvantage of these crosslinking agents, especially glutaraldehyde [33], benzaldehyde [34] and glyoxal is their toxicity to human tissues even at small traces [35], which has limited the use of chitosan hydrogels as scaffolds for drug delivery.

However, this paper discusses the recent trends in drug delivery systems (DDS) applications using macroscopic hydrogels. Hydrogel has received extensive attention due to its interconnected cross-linked porous hydrophilic polymer networks which can absorb large amounts of water or biological fluids. Additionally, hydrogels can be divided into three categories according to their size: macroscopic gels, nanogels (<200 nm), and microgels (0.5–10 μm). Hydrogels are promising, fashionable, intelligent and "smart" drug delivery vehicles that meet specific requirements for targeting drugs to specific sites and controlling drug release. The hydrogel-based drug carrier loaded with 5-fluorouracil (5-FU) drug for an up to 36 days sustained delivery has been studied by Xueyun Chen et al. [36].

Hydrogels are trendy, promising, intelligent and 'smart' drug delivery vehicles have become a great search field for targeting drugs to the specific sites and controlling drug release. Among several hardware platforms, ferrogels (FG) have a high potential for use in drug delivery. Ferrogels (FG) are consisting mainly of a polymer matrix embedded with magnetic micro and nano-particles (Fe3O4) [37–39]. Upon the application of an external magnetic field, the polymer matrix of the ferrogel can deform due to the magnetic force generated by the embedded magnetic particles, which would allow actuation and magnetically driven drug release on demand. The main advantage of ferrogels is that a larger quantity of drug can be loaded, compared to that transported by simple magnetic dispersion nanoparticles.

Ferrogel (FG) are typically prepared by incorporating magnetic particles into hydrogels [40]. Magnetic nanoparticles (Fe3O4) shown in **Figure 1**, have attracted much attention in the last few years as carriers for drug delivery systems. The potential use of nanoparticles as drug carriers has been presented in recent years as a major challenge, as nanoparticles have been designed to improve pharmacological and therapeutic effects in terms of reducing their toxic side effects. Besides, magnetite (Fe3O4) is considered as an important type of magnetic material with cubic inverse spinel structure. This property makes it very interesting because of its wide field of use, including magnetic recording, ferrofluid [41], catalyst [42] and some biomedical applications like magnetic resonance imaging (MRI) [43], bio separation [44], in addition to drug delivery system and therapeutic hyperthermia as well, to treat cancer and tumors [45]. Several methods have been developed recently

**Figure 1.** *Model of crystal structure of magnetite (Fe3O4) and spherical Fe3O4 nanoparticles.*

*Chitin and Chitosan - Physicochemical Properties and Industrial Applications*

their ability to target when an external magnetic field is applied [5].

wastewater treatment and agricultural sectors [13].

estimates 27 million cases of cancer and 17 million deaths disease for the year 2030 [1]. Therefore, study on cancer treatment has attracted many scientists. Among therapies, cancer chemotherapy is widely used despite its disadvantages. Chemotherapy usually causes serious side effects because of the low selectivity of anti-cancer drugs, which affects not only cancer cells but also normal cells [2]. Thus, increasing attention is being paid to targeted drug delivery systems, which have been used to increase the efficiency of drug delivery to specific tissues and to decrease the associated side effects. The most efficient solution is to use nanoparticles embedded in the hydrogel; this innovative-targeted drug delivery strategy involves coupling the drug to magnetic nanoparticles (NPs) that can be guided to the target using external magnetic fields [3]. Once they reach the target, the nanoparticles release the drugs under the influence of an alternating magnetic field [4]. Nanoparticle (NP) targeting has shown great potential for cancer drug delivery applications over the past decade. From nanoparticle targeting, magneto-particle have been widely studied because of

An increasing population causes serious environmental pollution, waste production is also increasing and major proportion of by-products generated by contemporary food remains underused which may often contain precious substances. The crucial problem confronting by industries and society in food processing is the elimination of food waste. Chitin is an important natural resource and the world's annual production of it is approximately 1010–1012 tons [6]. This latter is principally produced by mollusks, arthropods (crustaceans and insects) and fungi [7]. However, chitin and its derivatives have a high economic impact due to their numerous applications in the pharmaceutical [8], food [9, 10], cosmetics [11], textile [12],

In the past few decades, drug delivery systems (DDS) have been of great interest and resulted in many efforts to realize the effectiveness and targeted drug delivery tendency as well as to reduce the associated side effects [14]. However, DDS provide several advantages as compared to conventional dosages in terms of improved efficacy, reduced toxicity, improved patient compliance, and convenience [15]. Thus, the carriers used for drug release are generally biodegradable polymers which

On the other hand, with the rapid development of technology much attention has been given to use biopolymer based hydrogels in many applications including pharmaceuticals [17, 18], cosmetics [19], agriculture [20] and biotechnology [21, 22]. However, porous biomaterials fabricated from natural polymers "chitosan" were given significant attention for years. Chitosan is a unique natural cationic biopolymer produced by N-deacetylation of chitin and is the second most abundant natural polymer after cellulose [23]. Chitosan has been widely used in the biomedical field due to its superior properties including good biodegradability [24], biocompatibility [24], low toxicity [25, 26], mucoadhesive properties [27], antibacterial activity [28] and low cost [24, 29]. Chitosan is an excellent candidate for different applications particularly it has been employed in various FDA (Food and Drug Administration) approved biomedical applications. The -NH2 group of the (CS) chains is a pH-sensitive polymer with pKa around 6.5 due to variation of charge density at the pH range of 6–6.5, which is useful for wide range of pharmaceuticals applications. The pH value of the soluble-insoluble transition in the range 6–6.5 [30]. At pH levels beneath the pKa, high charge density of chitosan results in polyelectrolyte formation, in contrast at neutral pH, the low charge density of chitosan eases the intracellular release of biomolecules and contributes to its low cytotoxicity [31]. Chitosan has increasingly been used in the pharmaceutical field as it is one of the excellent choices for the Schiff's base linkages to form an injectable hydrogel due to the nature of abundant amino groups on its backbone. Hydrogels from chitosan

are extensively used for designing the control drug delivery systems [16].

**4**

#### **Figure 2.**

*Schematic representation of magnetic drug delivery system under the influence of external magnetic field.*

for preparing magnetic nanoparticles, such as co-precipitation [46], sol–gel [47], solvothermal [48], sonochemical and chemical vapor deposition phase (CVD) [49]. Among these methods, co-precipitation is considered as the simplest, most efficient, and most economic method.

Ferrogels characterized by the presence of magnetic particles incorporated in polymer gels, are the subject of extensive research due to those magnetic particles and magnetic fields which have an extended application and clinical acceptance [50, 51]. Recent studies have shown controlled release of many drugs from ferrogels subject to magnetic fields [52, 53]. Ferrogels (FG) have made also injectable and biodegradable. However, typical drug delivery ferrogels have a disadvantage due to the cross-linking agent toxicity, which limits the macroporous biomaterials synthesis [37].

There are only a few reports in the literature on the synthesis of Fe3O4 by coprecipitation method. In this paper, a macroporous ferrogel which is sensitive to magnetic field was studied. Furthermore, we are probably the first scientific team that reports the preparation of novel hydrogels and ferrogels based on chitosan and oxidized chitosan as cross-linking agent embedded Fe3O4/drug (5-FU, caffeine and ascorbic acid). **Figure 2** shows the magnetic drug delivery system under the influence of external magnetic field. The kinetics and in-vitro drug release profile of the drugs were studied in PBS pH (7.4) buffered solution at 37°C.
