**3. Oral peptide delivery**

The physiological barriers in the GIT responsible for protecting the body from the entry of pathogens. These barriers may reduce the bioavailability of the

**59**

**Figure 4.**

*Physiological barriers to oral protein and peptide delivery (adapted from [53]).*

*Chitosan-Based Oral Drug Delivery System for Peptide, Protein and Vaccine Delivery*

protein. The barriers aforesaid include biochemical, cellular, and mucus barriers

The entire GIT has been coated with mucus. Mucus also promotes a physical barrier between the lining of epithelial and lumen [54]. It contains mucin protein which secretes proteolytic enzymes and traps peptide drugs through electrostatic

The epithelium of the GIT consists of an intestinal epithelial stem and microfold cells (M-cell) [48]. These cells are responsible for controlling protein uptake from the gut lumen into the bloodstream. Since protein drug is a macromolecule, the presence of protein complexes between adjacent epithelial cells prevents paracellular transport of drug [56]. Meanwhile, transcellular transport is limited only to highly lipophilic molecules, unless the transportation is mediated by P-gp [57].

*DOI: http://dx.doi.org/10.5772/intechopen.95771*

(**Figure 4**) [53].

interaction [55].

*Chitosan-Based Oral Drug Delivery System for Peptide, Protein and Vaccine Delivery DOI: http://dx.doi.org/10.5772/intechopen.95771*

protein. The barriers aforesaid include biochemical, cellular, and mucus barriers (**Figure 4**) [53].

The entire GIT has been coated with mucus. Mucus also promotes a physical barrier between the lining of epithelial and lumen [54]. It contains mucin protein which secretes proteolytic enzymes and traps peptide drugs through electrostatic interaction [55].

The epithelium of the GIT consists of an intestinal epithelial stem and microfold cells (M-cell) [48]. These cells are responsible for controlling protein uptake from the gut lumen into the bloodstream. Since protein drug is a macromolecule, the presence of protein complexes between adjacent epithelial cells prevents paracellular transport of drug [56]. Meanwhile, transcellular transport is limited only to highly lipophilic molecules, unless the transportation is mediated by P-gp [57].

**Figure 4.** *Physiological barriers to oral protein and peptide delivery (adapted from [53]).*

*Chitin and Chitosan - Physicochemical Properties and Industrial Applications*

**1.5 The use of chitosan to improve drug delivery system**

from the nanoparticulate system.

in enteric-coated drugs [38, 43].

ness of the drugs in eradicating the infection [15].

**2. The properties of protein and peptide**

angiotensin, vasopressin and oxytocin [4].

residues through sulphhydryl groups [52].

**3. Oral peptide delivery**

chains of amino acid interacts with each other [51].

bioavailability.

The polymeric chitosan chain will start to detangle. The swelling polymer will form pores which allow drugs to diffuse out of the nanoparticulate system [6, 43, 47]. Therefore, the water solubility of chitosan is crucial in the mechanism of drug release

Oral drug administration is the most convenient route, especially among the elderly and children. Unfortunately, some drugs and vaccines cannot withstand the physiological barrier of GIT. In the presence of mucus, proteolytic enzymes, and first-pass metabolism by the liver, drugs tend to be degraded or converted into inactive metabolites [48]. Some drugs will be excreted in the urine lead to low

Due to the challenges aforesaid, chitosan and its derivatives have been used in the development of nanotechnology to improve oral drug delivery [25, 30]. It encapsulates drugs to protect them from degradation in the GIT environment. As a consequence of its excellent biodegradable, biocompatibility, and non-toxic properties, chitosan promotes a stimuli-responsive release of drugs. It allows active ingredients to be released from the formulation in a controlled manner, specifically

Due to its antimicrobial properties, it was used in the delivery of oral antibiotics to eradicate Gram-negative bacteria such as *E. coli* [49]. This approach not only improves the bioavailability of antibiotic in the body but also indirectly enhance the effective-

A peptide is made up of short polymers of ⍺-amino acid, which is around 20 to 50 amino acids. The function of small peptides depends on the functional group of various amino acids. Examples of active peptides are glutathione, bradykinin,

Protein is a macromolecular and high molecular weight polypeptide, which is made up of long-chain amino acids (more than 50) arranged in a linear chain through peptide bonds [50]. It can exist in four different structural conformations such as primary, secondary, tertiary, and quaternary. The formation of these structures is dependent on the intermolecular interaction between functional groups of

The covalent bonds are strong bonds which include peptide bonds and disulfide bonds [51]. Peptide bonds are interactions between two consecutive amino acids through amino and carboxyl groups. Meanwhile, disulfide bonds link two cysteine

On the other hand, non-covalent bonds are weak bonds that include hydrogen, electrostatic and hydrophobic bonds. Hydrogen bonds link two different peptides with the hydrogen atom of the N-H group and oxygen of the carboxylic group. Hydrophobic bonds will occur if the hydrophobic nature between non-polar side

The physiological barriers in the GIT responsible for protecting the body from the entry of pathogens. These barriers may reduce the bioavailability of the

amino acids [51], through covalent bonds or non-covalent bonds.

**58**

Due to the physical and chemical instability of protein in the GIT, they would not achieve an acceptable therapeutic bioavailability. The nature of the GIT as great physiology to digest food will be a barrier for protein drugs to penetrate through the membrane. The challenges and strategies to improve the protein drug delivery through oral administration need to be considered to ensure the drug achieves adequate therapeutic concentration in the body [58].
