Regioselective succinylation and gelation behavior of glycol chitosan

Abstract

Chitosan is normally acylated and subsequently conjugated with drugs for biomedical applications. This study examined the relationship between the succinylation and gelation behaviors of glycol chitosan. Glycol chitosan was acylated with succinic anhydride under a wide variety of reaction conditions, such as different molar ratios of succinic anhydride to glucosamine, different methanol content in the reaction media, and different reaction temperatures. Among these reaction parameters, the methanol content in the solvent played an important role in determining the regioseletive succinylating site. N-succinylation and N-N cross-linking occurred regardless of the reaction conditions. However, O-succinylation was observed under specific conditions, i.e. a methanol content > 0.6 (v/v) and a reaction temperature > 25 °C. O-succinylation accelerated the N-O cross-linking of glycol chitosan, and led to gelation. The N-succinylated glycol chitosans were water-soluble, whereas the N- and O-succinylated glycol chitosans formed a gel. These physico-chemical structural differences in the succinylated glycol chitosans would definitely influence subsequent drug-conjugation reactions and consequently the drug loading and release kinetics.