Development of novel formulations for mucosal delivery of protein ...

male wistar rats after induction of colitis disintegrated specifically in the large intestines as
compared to the control formulation (absence of chitosan) which demonstrated absorption of
the drug in the small intestines.
Chitosan has mucoadhesive properties and is often exploited to enhance the residence
time of a drug on the mucosal membrane thereby increasing the drug bioavailability. A
comparison between chitosan and other commonly used polymeric excipients indicates that
the cationic polymer has higher bioadhesivity compared to other natural polymers, such as
cellulose, xanthan gum, and starch (Kotze et al., 1999).
1.6.2 Pharmaceutical and medicinal uses of chitosan
A number of clinical studies have reported the use of chitosan as cell scaffolds in
tissue engineering, nerve regeneration tubes, and cartilage regeneration (Khor & Lim, 2003,
Freier et al., 2005, Mwale et al., 2005). In addition, it has been used extensively as a
biomaterial, owing to its immunostimulatory activities (Gorbach et al., 1994), anticoagulant
properties, antimicrobial and antifungal action (Rabea et al., 2003) and for its action as a
promoter of wound healing in the field of surgery (Khan et al., 2000). Because of its
biocompatibility and biodegradation properties (Vandevord et al., 2002), chitosan has been
used in a variety of pharmaceutical formulations, primarily for the purpose of controlled drug
delivery (Agnihotri et al., 2004), such as mucosal (Illum et al., 2001, Van Der Lubben et al.,
2001, Read et al., 2005), buccal (Giunchedi et al., 2002), and ocular (De Campos et al., 2004)
delivery of drugs.
Due to its cationic nature, chitosan is capable of opening tight junctions in a cell
membrane. This property has led to a number of studies to investigate the use of chitosan as a
permeation enhancer for hydrophilic drugs such as peptides that may otherwise have poor oral
bioavailability (Thanou et al., 2000). Because the absorption enhancement is caused by
interactions between the cell membrane and positive charges on the polymer, the phenomenon
is pH and concentration dependant. Furthermore, increasing the charge density on the
polymer would lead to higher permeability. This has been studied by quaternizing the amine
functionality on chitosan (Hamman et al., 2003). The amine functionality is further explored
in the proceeding section.
30