An Investigation into the Digestibility of Chitosan by Human Colonic Bacteria

The suitability of chitosan (non-crosslinked and crosslinked by glutaraldehyde) for colonic drug delivery was assessed by incubation of chitosan films in human faecal slurry and assessment of the film’s disappearance with time. It was found that non-crosslinked chitosan, was digested by colonic bacteria, but crosslinked chitosan was not. Introduction: Polysaccharides, such as amylose, guar gum, pectin and chitosan (Basit, 2005) are increasingly being investigated for the delivery of drugs to the colon. An essential feature of these potential drug delivery systems is non-degradation by small intestinal digestive enzymes, but digestion by the enzymes produced by the colonic microflora. Thus, they should prevent drug release in the small intestine, and allow drug release in the colon. Chitosan is being investigated as it is biodegradable, biocompatible and has low oral toxicity. There are several investigations into the suitability of chitosan for colonic delivery (Tozaki et al., 1997; Zambito et al., 2005) but all investigations to date have used rat caecal contents to assess the colonic release. This may not be directly comparable to human colonic contents or faecal material. Work has shown that chitosan is degraded to different extents in different species, such as dogs (Okamoto et al., 2001), rabbits, hens and sheep (Hirano et al., 1990). Hence, it cannot be assumed that chitosan is sufficiently digested by human colonic microflora. Before investigating the potential of chitosan as a colonic delivery system, it is essential to assess whether the human colonic microflora is capable of digesting the material. The process of microfloral digestion is one of fermentation, in which the anaerobic bacteria break down substrates to produce energy. Chitosan, a weak base (pKa 6.2-7.0), is a [(1,4) 2 amino-2-deoxy-beta-d-glucan], whose structure is shown in Figure 1. It is obtained by the alkaline deacetylation of chitin, which is the second most abundant polysaccharide in nature, after cellulose. It is found in the exoskeletons of crustaceans and insects which are not substantial components of the human diet. Human colonic bacteria may not therefore normally produce enzymes capable of digesting chitin and chitosan. The latter is structurally similar to cellulose, which has been shown not to be fermented in the human colon. Figure 1 Structure of Chitosan