Chitosan is a natural polymer whose bioadhesive properties make it a useful material for filming over and protecting damaged or sensitive mucosae. Much effort has been expended to develop this employ, and new applications are in the offing. The aim of the present study was to optimize the synthesis under sonochemical conditions of water-soluble chitosan tetraalkylammonium salts and to assess the mucoadhesive properties of the resulting water-soluble cationic polyelectrolytes. Aqueous solutions of several tetralkylammonium chitosan derivatives, viz. N-trimethyl- (1), N-diethylmethyl- (2), N-carboxymethyl- (3) and N-[N,N-diethylaminomethyl(diethyldimethylene ammonium)(n)]methylchitosan (4) were tested along with the parent biopolymer and its citric acid salt (5), both at neutral and acidic pH. We used a published technique for evaluating in vitro bioadhesion to isolated buccal cells, a mucosal model that can predict bioadhesive behavior in vivo. Derivatives 1 and 4 gave the best results.