Chitosan for enhanced intestinal permeability: Prospects for derivatives soluble in neutral and basic environments

In this study the effects of two chitosan salts, namely chitosan hydrochlor ide and chitosan glutamate (0.5 and 1.5% w/v), on the transepithelial elect rical resistance (TEER) and permeability of Caco- cell monolayers, using th e radioactive marker [C-14]-mannitol, were investigated in a slightly acidi c (pH 6.2) and neutral (pH 7.3) environment. Both salts are soluble in acid ic conditions up to a concentration of 1.5% w/v and solutions of this stren gth, at a pH of 6.2, caused a pronounced lowering in the TEER of Caco-2 cel l monolayers in the order of 70+/-1% (chitosan glutamate) and 77+/-3% (chit osan hydrochloride), 20 min after incubation started. In agreement with the TEER results the transport of the radioactive marker, [C-14]-mannitol, was increased 25-fold (chitosan glutamate) and 36-fold (chitosan hydrochloride ), respectively, at this pH. However, at a pH of 7.4 both salts are insolub le and prove to be ineffective since no reduction in the TEER values or inc rease in the transport of [C-14]-mannitol were found. The results show that these chitosan salts are potent absorption enhancers in acidic environment s. We conclude that there is a need for chitosan derivatives with increased solubility, especially at neutral and basic pH values, for use as absorpti on enhancers aimed at the delivery of therapeutic compounds in the mon basi c environment of the large intestine and colon. (C) 1998 Elsevier Science B .V. All rights reserved.