In vitro evaluation of the viscoelastic properties of chitosan–thioglycolic acid conjugates

Abstract

The aim of this study was to evaluate the viscoelastic properties of chitosan–thioglycolic acid conjugates with different amounts of thiol groups immobilized on the polymer. The modification of chitosan was achieved via the covalent attachment of thioglycolic acid mediated by a carbodiimide. Chitosan–thioglycolic acid conjugates displaying 120, 209 and 439 μM thiol groups per gram of polymer were synthesized. The rheological properties of the three different conjugates were investigated. The elastic properties of the gels were found to increase significantly at pH 5.5. After 6 h the elastic modulus G′ of chitosan–TGA 120, chitosan–TGA 209 and chitosan–TGA 439 gels increased 7-, 32- and 168-fold, respectively. In parallel the formation of disulfide bonds was observed. Accordingly, proof of principle that chitosan modified by the introduction of thiol groups has in situ gelling properties due to the formation of inter- and intramolecular disulfide bonds at physiological pH values is provided. Based on their in situ gelling properties, chitosan–thioglycolic acid conjugates seem to be very promising new excipients for liquid or semisolid formulations which should stabilize themselves once applied on the site of drug delivery.