**1.2 Characterisation of chitin and chitosan**

*Chitin and Chitosan - Physicochemical Properties and Industrial Applications*

needed to enhance drug effectiveness and patient compliance.

the drug from enzymatic degradation [9].

vaccines bioavailability.

**1.1 Chitosan**

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

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

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

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

**52**

**Figure 1.**

*The N-deacetylation of chitin into chitosan.*

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 drug delivery system [9].

Some factors affect chitosan properties, including the degree of deacetylation, 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 intramolecular hydrogen bonds [12].

## *1.2.1 Degree of deacetylation and molecular weight of chitosan*

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

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 polymer [16].

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


**Table 1.**

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

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

usable energy in the system. Loss of energy means the reaction in the system tends to be spontaneous.

The α-chitin crystalline form exhibit lower water solubility as compared to β-chitin. The shorter polymeric chain of low molecular weight chitosan (LMWC) is unlikely to aggregate [11]. Interaction between molecules declines due to the formation of the hydrogen bonds is limited. A short chitosan chain contains a low number of amino groups [20].
