Synthesis of cross-linked N-(2-carboxybenzyl)chitosan pH sensitive polyelectrolyte and its use for drug controlled delivery

N-(2-Carboxybenzyl)chitosan (CBCS) polyelectrolyte was synthesized via a Schiff reaction of chitosan with 2-carboxybenzaldehyde, followed by reduction of the imine derivative with sodium borohydride. The polyampholyte chitosan derivative was cross-linked with glutaraldehyde leading to the formation of a pH-sensitive hydrogel. All prepared materials were characterized by FTIR, UV and H-1 NMR spectroscopies. The swelling behavior of the cross-linked N-(2-carboxybenzyl)chitosan hydrogel (CBCSG) was studied in aqueous solutions of varied pH (1, 5, 7 and 9). It was found that CBCSG swelled more in acidic solutions than in alkaline ones. Drug loading of fluconazole (a sparingly water-soluble drug) in CBCSG was prepared using the solvent evaporation method. WAXD data revealed that the drug was amorphous in the prepared formulations with 20% (w/w) drug content or less and crystalline at higher loading. Release of fluconazole from CBCSG was effectively sustained, indicating the suitability of the CBCSG to be used as a controlled-release system of fluconazole. The release rate was found to depend on drug loading and the pH of the release medium, which controlled the swelling capacity of the gel during drug release. (C) 2010 Elsevier Ltd. All rights reserved.