Viscoelastic properties of a new in situ gelling thiolated chitosan conjugate

The aim of this study was the synthesis of a new thiolated chitosan conjugate and the evaluation of its viscoelastic properties in vitro. The modification of chitosan was achieved by covalent attachment of isopropyl-S-acetylthioacetimidate to chitosan. The resulting conjugate (chitosan-TEA; chitosan-thioethylamidine) exhibited 300.7+/-27.4 micromol thiol groups per gram polymer and no disulfide bond. For rheological studies, the pH of 0.5% and 1% polymer solutions was adjusted to 6.5 in order to simulate a physiological pH-level. Both, 0.5% and 1% chitosan-TEA solutions showed the transition from sol to gel within 30 min. Within 6 h of incubation, the storage modulus of 0.5% and 1% chitosan-TEA increased 3354-fold and 6199-fold, whereas the loss modulus increased 11-fold and 38-fold, respectively. Frequency sweep measurements demonstrated an increase in crosslinking of the thiolated polymer as a function of time. The formation of inter- and/or intramolecular disulfide bonds was monitored indirectly via determining the decrease of thiol groups. Unmodified chitosan did not exhibit in situ gelling properties. The release of a fluorescent marker being incorporated in a 0.5% chitosan-TEA solution was significantly (p<0.001) slower, when the formulation was preincubated for one hour and consequently already highly crosslinked. The polymer generated within this study represents a promising novel tool for various drug delivery systems, where in situ gelling properties are advantageous.