Synthesis, characterization, mucoadhesion and biocompatibility of thiolated carboxymethyl dextran–cysteine conjugate

Abstract

This study was aimed at improving the mucoadhesive properties of carboxymethyl dextran by the covalent attachment of cysteine. Mediated by a carbodiimide, l-cysteine was covalently attached to the polymer. The resulting CMD–cysteine conjugate (CMD- 273 conjugate) displayed 273 ± 20 μmol thiol groups per gram of polymer (mean ± S.D.; n = 3). Within 2 h the viscosity of an aqueous mucus/CMD- 273 conjugate mixture pH 7.4 increased at 37 °C by more than 85% compared to a mucus/carboxymethyl dextran mixture indicating enlarged interactions between the mucus and the thiolated polymer. Due to the immobilization of cysteine, the swelling velocity of the polymer was significantly accelerated ( p < 0.05). In aqueous solutions the CMD- 273 conjugate was capable of forming inter- and/or intramolecular disulfide bonds. 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 15 min, whereas tablets of the CMD- 273 conjugate remained stable for 160 min (means ± S.D.; n = 3). Results from LDH and MTT assays on Caco-2 cells revealed 4.96 ± 0.98% cytotoxicity and 94.1 ± 0.9% cell viability for the CMD- 273 conjugate, respectively. Controlled release of model compound from CMD- 273 conjugate tablets was observed over 6 h. These findings suggest that CMD- 273 conjugate is a promising novel polymer for drug delivery systems providing improved mucoadhesive and cohesive properties, greater stability and biocompatibility.