Synthesis and characterization of a biocompatible chitosan–based hydrogel cross–linked via ‘click’ chemistry for controlled drug release

Abstract

A chemically cross–linked chitosan–based hydrogel was successfully synthesized through Diels–Alder (DA) reaction and characterized. The final product was obtained after different steps; on the one hand, furan–modified chitosan (Cs–Fu) was synthesized by the reaction of furfural with the free amino groups of chitosan. On the other hand, highlighting the novelty of the present research, maleimide–functionalized chitosan (Cs–AMI) was prepared by the reaction of a maleimide–modified aminoacid with the amino groups of chitosan through amide coupling. The two complementary chitosan derivatives were cross–linked to the final hydrogel network. Both modification reactions were confirmed by FTIR and 1H NMR, obtaining a degree of substitution (DS) of 31% and 26% for Cs–Fu and Cs–AMI, respectively. The as–designed hydrogel was analyzed in terms of microstructure, swelling capacity and rheological behaviour. The hydrogel showed pH–sensitivity, biocompatibility and inhibitory bacterial activity, promising features for biomedical applications, particularly for targeted–drug delivery.