**3. Protein-based encapsulation**

#### **3.1 Proteins in micro- and nanoencapsulation**

Protein-based delivery systems can be synthesized via different kinds of animal and plant proteins using a range of different production methods. A fabricator should pick the most fitting protein for a certain application, after making sure of all safety requirements. The main elements influencing the selection of the protein and encapsulation methods are:

for example, is the most abundant plasma protein, which makes it non-toxic, biodegradable, and non-immunogenic. It has also good connectivity to many drugs and it is extremely robust to various conditions. Gelatin and collagen possess many carboxyl groups with possible crosslinking functions. These parameters are important for selecting the nanoparticles synthesis method. The protein selection depends on drug properties, and on the target of the nanoparticles to be prepared. The selected protein properties such as functionality, molecular weight, and hydrophobicity can affect particle size, drug loading and loading efficiency, and dissolution or release profile of the drug to the surrounding environment of the nanoparticles. The proteins have the chance to target a specific place in vivo and secure the encapsulated active molecules from biodegradation and undesirable metabolism - **Figure 6**. Protein nanoparticles, however, have unique properties when compared to other nanoparticles since they are extracted from natural origins that exist in nature, easy to handle, and most importantly they are non-toxic as they do not leave

*Natural Polymers in Micro- and Nanoencapsulation for Therapeutic and Diagnostic…*

The physicochemical properties of proteins such as isoelectric point (pI), chemical compositions, denaturation thermal temperature (Tm), and solubility are necessary for the fabrication of the protein-based micro- and nanoencapsulation delivery systems (**Table 4**) [82–90]. Some micro- and nanoencapsulation processes use protein as a wall material to act as a barrier which is used to protect bioactive agents against the surrounded environmental conditions including pH, temperature, moisture, and oxygen and form stable capsules (they are in a range size between few micrometers and millimeters in microencapsulation methods and from 10 nanometers to one micrometer in nanoencapsulation methods) with high encapsulation efficiency (EE) due to their excellent gel, film and emulsifying formation properties, and promising improvements such as water solubility, stability, and bioavailability [91, 92]. Besides,

undesirable biodegradation products.

**Figure 5.**

**Figure 6.**

**71**

*3.1.2 Physicochemical properties of proteins*

*Drug loading and release from protein-based nanoparticles.*

*Schematic illustration of encapsulation of bioactive agents.*

*DOI: http://dx.doi.org/10.5772/intechopen.95402*


**Figure 5** is a schematic illustration of polymeric encapsulation of bioactive agents.

#### *3.1.1 Applications and clinical usage*

Protein-based nanoparticles (PBNs), recently reported, are of great interest due to their various advantages. They confirmed their high activity in both clinical and medicinal fields. Several formulations have been developed and suggested as potential future therapeutic products [80]. Besides, some PBNs have been officially accepted by US food and drug administration [81]. In addition, protein-based nanoparticles functional groups (e.g. carboxylic and amino groups) facilitate the particles surface modification, which makes them suitable for tumor targeting strategies. On the other hand, protein-based nanoparticles (PBNs) surface can be modified by attachment of targeting ligands such as peptides, antibodies, vitamins, hormones, and enzymes. These surface modifications allow specific targeting and accumulation of the particles at the desired site such as a tumor. Each protein tends to encapsulate either hydrophobic or hydrophilic molecules. Gelatin, silk, gliadin, and legumin have higher encapsulation efficiency for hydrophilic drugs. While collagen, casein, and zein proteins have higher encapsulation efficiency for hydrophobic drugs. Albumin, however, can bioconjugate with hydrophilic drugs and interact with highly hydrophobic drugs. Besides, each protein has some characteristics that enhance its selectivity to be a better carrier for a certain drug. Albumin,

*Natural Polymers in Micro- and Nanoencapsulation for Therapeutic and Diagnostic… DOI: http://dx.doi.org/10.5772/intechopen.95402*

**Figure 5.** *Schematic illustration of encapsulation of bioactive agents.*

of urea. The detection ability of the sensor was determined by the color strength

dinates. The dye and enzyme-loaded crosslinked alginate microparticles coated cotton sensor strips were effectively employed to determine unknown concentrations of urea. The spectroscopic parameters indicated the microencapsulated sensor displayed a detection range of 0.1 ppm to 250 ppm. **Tables 2** and **3** indicate applications based on micro- and nano-encapsulation utilizing natural polysaccharides as

Protein-based delivery systems can be synthesized via different kinds of animal

and plant proteins using a range of different production methods. A fabricator should pick the most fitting protein for a certain application, after making sure of all safety requirements. The main elements influencing the selection of the protein and

a. Nanocarrier chemical or physical compatibility with food components.

b. Nanocarrier stability under processing, storage, or during its application.

c. Possible release mechanism(s) and conditions affecting the rate of release.

e. Cost-effectiveness of nanocarriers when synthesized on a large scale for real

Protein-based nanoparticles (PBNs), recently reported, are of great interest due to their various advantages. They confirmed their high activity in both clinical and medicinal fields. Several formulations have been developed and suggested as potential future therapeutic products [80]. Besides, some PBNs have been officially accepted by US food and drug administration [81]. In addition, protein-based nanoparticles functional groups (e.g. carboxylic and amino groups) facilitate the particles surface modification, which makes them suitable for tumor targeting strategies. On the other hand, protein-based nanoparticles (PBNs) surface can be modified by attachment of targeting ligands such as peptides, antibodies, vitamins, hormones, and enzymes. These surface modifications allow specific targeting and accumulation of the particles at the desired site such as a tumor. Each protein tends to encapsulate either hydrophobic or hydrophilic molecules. Gelatin, silk, gliadin, and legumin have higher encapsulation efficiency for hydrophilic drugs. While collagen, casein, and zein proteins have higher encapsulation efficiency for hydrophobic drugs. Albumin, however, can bioconjugate with hydrophilic drugs and interact with highly hydrophobic drugs. Besides, each protein has some characteristics that enhance its selectivity to be a better carrier for a certain drug. Albumin,

**Figure 5** is a schematic illustration of polymeric encapsulation of bioactive

d. Biodegradability of the protein-based nanocarrier in the body.

and b⁎ color coor-

and the International Commission on Illumination – CIE L\*, a⁎,

*Nano- and Microencapsulation - Techniques and Applications*

encapsulating materials.

encapsulation methods are:

applications.

*3.1.1 Applications and clinical usage*

agents.

**70**

**3. Protein-based encapsulation**

**3.1 Proteins in micro- and nanoencapsulation**

for example, is the most abundant plasma protein, which makes it non-toxic, biodegradable, and non-immunogenic. It has also good connectivity to many drugs and it is extremely robust to various conditions. Gelatin and collagen possess many carboxyl groups with possible crosslinking functions. These parameters are important for selecting the nanoparticles synthesis method. The protein selection depends on drug properties, and on the target of the nanoparticles to be prepared. The selected protein properties such as functionality, molecular weight, and hydrophobicity can affect particle size, drug loading and loading efficiency, and dissolution or release profile of the drug to the surrounding environment of the nanoparticles. The proteins have the chance to target a specific place in vivo and secure the encapsulated active molecules from biodegradation and undesirable metabolism - **Figure 6**. Protein nanoparticles, however, have unique properties when compared to other nanoparticles since they are extracted from natural origins that exist in nature, easy to handle, and most importantly they are non-toxic as they do not leave undesirable biodegradation products.

### *3.1.2 Physicochemical properties of proteins*

The physicochemical properties of proteins such as isoelectric point (pI), chemical compositions, denaturation thermal temperature (Tm), and solubility are necessary for the fabrication of the protein-based micro- and nanoencapsulation delivery systems (**Table 4**) [82–90]. Some micro- and nanoencapsulation processes use protein as a wall material to act as a barrier which is used to protect bioactive agents against the surrounded environmental conditions including pH, temperature, moisture, and oxygen and form stable capsules (they are in a range size between few micrometers and millimeters in microencapsulation methods and from 10 nanometers to one micrometer in nanoencapsulation methods) with high encapsulation efficiency (EE) due to their excellent gel, film and emulsifying formation properties, and promising improvements such as water solubility, stability, and bioavailability [91, 92]. Besides,

**Figure 6.** *Drug loading and release from protein-based nanoparticles.*
