**1. Introduction**

The extent of drug bioavailability has been shown to be influenced by the route of drug administration. Oral drug route needs travelling through the continuous passageway of the GIT, which makes them susceptible to the harsh environment of GIT. Drugs intended for administration via this route can be formulated in a variety of dosage forms, such as tablets, capsules, solutions, and powders.

Due to its high patient compliance and ease of administration, the oral route of administration is preferred among other routes. Self-administration is possible with great compliance and reduced risk in developing systemic side effects, which is the major concern in the parenteral route [1]. Despite that, the oral delivery system approaches for certain drugs are challenging, especially the delivery of peptide drugs and vaccines [2].

The normal physiological functions of GIT are to digest food and to interfere with pathogen entry. These functions need to be considered as peptide drugs and vaccines tend to be digested together with food in the presence of digestive

#### *Chitin and Chitosan - Physicochemical Properties and Industrial Applications*

enzymes. The highly acidic pH in the stomach and the presence of proteolytic enzymes such as protease and pepsin can cause protein degradation [1].

Furthermore, they will have difficulties in permeating the physical barrier of the mucus lining, which prevents pathogenic substances from penetrating the cell [3]. Owing to these challenges, protein and peptide drugs are suitable to be administered via parenteral routes such as intravenous or subcutaneous injection [4]. However, these routes require frequent administration with long-term use which will develop patient incompliance to medication [4]. In such a manner, the approach to improve the oral delivery of peptide drugs and vaccines by using suitable polymers are needed to enhance drug effectiveness and patient compliance.

Chitin is the second most abundant polysaccharide present in nature. However, it has more applications when converted to chitosan by partial deacetylation under alkaline conditions [5]. Chitosan is a positively charged polymer that can improve the bioavailability of the oral drug delivery system. It has been used to improve the formulation of peptide drugs, resulting in enhanced cell permeability, which allows an adequate therapeutic concentration of drugs into the systemic circulation [6].

For protein and peptide therapeutics, factors such as poor permeability, luminal, brush border, cytosolic metabolism, and hepatic clearance mechanisms result in their poor bioavailability from oral and non-oral mucosal routes [7]. Oral vaccination is prone to reduce the adequacy of vaccine to be recognised by the immune system due to the presence of gut microbiota and intestinal barrier. Peptide drugs and vaccines can be protected from the degradative barrier of the GIT by encapsulating the drugs into the polymeric chitosan as potential carrier material. The development of nanotechnology, such as nanoparticle systems to transport peptide drugs through the epithelial membrane has been established [6, 8]. Besides, the modification of chitosan is needed to exert its function as a polymer and to protect the drug from enzymatic degradation [9].

This work reviews the physicochemical properties and numerous applications of chitosan, describes its release mechanisms, challenges in oral peptides and vaccines delivery, and strategies to overcome these barriers to improve oral peptides and vaccines bioavailability.

#### **1.1 Chitosan**

Chitosan is a strong base with linear polysaccharides consisting of D-glucosamine, which contains amino groups [10]. The hydrolysis of chitin will produce chitosan through alkaline hydrolysis or N-deacetylation (**Figure 1**). Due to protonable amino groups presence in chitosan, this polymer can be easily

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**Table 1.**

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

dissolved in pH below 6.3. However, both chitosan and chitin are insoluble in an

Chitin or chitosan is highly available from different species of shrimps, prawns and crabs. These seafood shells release chitosan, which shows properties of antimi-

One of the differences between chitosan and chitin is the presence of amino groups. Amino group in chitosan exhibits high solubility in acidic medium and able to form complexes with metal ions. These positive charges interact with drugs and physiological barriers in the GIT, which is useful in the formulation design of the

Some factors affect chitosan properties, including the degree of deacetylation,

The degree of chitosan deacetylation will affect its biological activity, including swelling rate, molecular weight, crystallinity and polydispersity. The deacetylation process leads to the protonation of the amino groups [13]. A highly positive charge will improve the activity of chitosan as mucoadhesive permeation enhancing [14] and haemostatic agent [15]. Sometimes, the degree of deacetylation can be used to

The degree of deacetylation can influence the particle size and molecular weight

of chitosan [13]. The removal of the acetyl group in the structure of chitosan or chitin from deacetylation reduces the interaction between molecules. A low number of acetyl groups minimises the chain length, thus reducing the molecular weight of

The molecular weight of the polymer will influence the degree of swelling [17]. High molecular weight chitosan (HMWC) tends to have a higher cross-linking ability. Therefore, the drug-coated with HMWC tends to release more slowly [18]. This characteristic is favourable in sustained-release oral drug delivery. Generally, the lower the molecular weight, the higher solubility of chitosan is obtained [13, 19]. HMWC appears in α-chitin crystalline or antiparallel structure. The structure forms after the release of water, which leads to the loss of entropy during aggregation of the polymeric chain [13]. This phenomenon results in the loss of Gibbs free energy. Gibbs free energy (G) is a way to predict the amount of

**Degree of deacetylation Level Water solubility** 55–70% Low Completely insoluble 70–85% Middle Partly dissolved 85–95% High Good solubility 95–100% Ultrahigh Completely soluble

*Relationship between degree of deacetylation of chitosan and their water solubility [11].*

degree of substitution, and molecular weight [9, 11]. These factors should be considered before using chitosan as a polymer in a drug delivery system. Most of the chitosan applications are affected by these factors through intermolecular or

*1.2.1 Degree of deacetylation and molecular weight of chitosan*

estimate the water solubility of chitosan [11] as shown in **Table 1**.

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

**1.2 Characterisation of chitin and chitosan**

crobial and antioxidant activity.

drug delivery system [9].

the polymer [16].

intramolecular hydrogen bonds [12].

aqueous medium.

**Figure 1.** *The N-deacetylation of chitin into chitosan.*

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

dissolved in pH below 6.3. However, both chitosan and chitin are insoluble in an aqueous medium.

Chitin or chitosan is highly available from different species of shrimps, prawns and crabs. These seafood shells release chitosan, which shows properties of antimicrobial and antioxidant activity.
