Improvement in the mucoadhesive properties of alginate by the covalent attachment of cysteine

The purpose of the present study was to improve the mucoadhesive properties of alginate by the covalent attachment of cysteine. Mediated by a carbodiimide, L-cysteine was covalently linked to the polymer. The resulting thiolated alginate displayed 340.4+/-74.9 mu mol thiol groups per g conjugate (means+/-S.D.; n=4). Within 2 h the viscosity of an aqueous mucus/alginate-cysteine conjugate mixture pH 7.0 increased at 37 degreesC by more than 50% compared to a mucus/alginate mixture, indicating enlarged interactions between the mucus and the thiolated polymer. Tensile studies carried out on freshly excised porcine intestinal mucosa demonstrated a total work of adhesion (TWA) of 25.8+/-0.6 and 101.6+/-36.1 muJ for alginate and the alginate-cysteine conjugate, respectively (means+/-S.D.; n=5). The maximum detachment force (MDF) was thereby in good correlation with the TWA. Due to the immobilization of cysteine, the swelling velocity of the polymer was significantly accelerated (P<0.05). In aqueous media the alginate-cysteine conjugate was capable of forming inter- and/or intramolecular disulfide bends. Because of this crosslinking process within the polymeric network, the cohesive properties of the conjugate were also improved. Tablets comprising the unmodified polymer disintegrated within 49+/-14.5 min, whereas tablets of thiolated alginate remained stable for 148.8+/-39.1 min (means+/-S.D.; n=3). These features should render thiolated alginate useful as excipient for various drug delivery systems providing an improved stability and a prolonged residence time on certain mucosal epithelia. (C) 2001 Elsevier Science B.V. All rights reserved.