| Of all the approaches investigated to achieve colon-specific drug delivery, carriers that rely on microbial degradation by colonic bacteria to release drug have been shown to afford the required site specificity. Chitosan, a natural, non-toxic, biodegradable polysaccharide has received attention recently, for use as a potential component in colonic drug delivery carrier systems. Since chitosan refers to a family of polymers with different intrinsic properties, such as different molecular weight and degree of deacetylation, its susceptibility to microbial degradation may be influenced by its intrinsic properties and, in turn, the performance of its drug delivery system can be affected. The purpose of this research was to provide in vitro enzymatic assay results to characterize the degradation behavior of chitosan, to guide in formulation development and to evaluate and compare the performance of chitosan-based colonic drug delivery systems. The susceptibility of five chitosan samples to degradation by almond β-glucosidase, identified to have chitinase activity, and by rat cecal and colonic enzymes, whose activities are comparable to that in the human colon, was characterized. The results indicate that both enzyme systems could utilize chitosan a substrate and chitosan susceptibility to degradation was affected by both its molecular weight and degree of deacetylation, with a lower molecular weight and lower degree of deacetylation sample a more promising substrate. In light of such observations, an optimum product among the five chitosan samples was identified and a multiparticulate system, namely hydrogel beads of this chitosan sample, was proposed. The suitability of such a chitosan based delivery system for colon targeting was assessed in both enzyme systems and also under conditions simulating the pH and times likely to be encountered during intestinal transit to the colon. The results show that the chitosan hydrogel bead was still able to be degraded by the rat cecal and colonic enzymes, resulting in a substantial release of active, which indicates the potential of such a multiparticulate system to serve as a system capable of delivery specifically to the colon. Results suggest that chitosan is a polysaccharide worthy of pursuit in the development of colon-specific drug delivery systems. |
