An investigation into the digestion of chitosan (noncrosslinked and crosslinked) by human colonic bacteria

Chitosan salts are being investigated as materials for bacterially triggered colonic drug delivery, via the oral route, based on the assumption that they will be degraded by the enzymes produced by the human colonic bacteria. The actual susceptibility of chitosan to these enzymes is, however, unclear. The digestion of chitosan films (noncrosslinked, and crosslinked with glutaraldehyde or tripolyphosphate) by human colonic bacteria (using human faecal material) was therefore investigated, and in addition, their digestion by pancreatic enzymes (of porcine origin) was assessed. Noncrosslinked chitosan films were digested by both pancreatic and colonic enzymes within 4 h, while glutaraldehyde crosslinked chitosan films were resistant to both enzyme systems. In contrast, tripolyphosphate crosslinked chitosan films resisted pancreatic digestion, but were susceptible to faecal digestion over the same 4 h time period. As expected, lowering crosslinker concentration and increasing incubation time (to 18 h) allowed greater digestion. The difference between the crosslinkers is attributed to the mechanism of crosslinking, and the associated degree of film swelling in an aqueous environment, Swelling studies in acidic conditions suggest that only glutaraldehyde or higher concentrations of tripolyphosphate would be able to prevent film dissolution in gastric conditions. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:3820-3829, 2008.