Synthesis of cationic chitosan hydrogel with long chain alkyl and its controlled glucose-responsive drug delivery behavior

Abstract

A novel glucose-responsive controlled drug release system based on cationic chitosan derivative (HDCC) with long chain alkyl was synthesized by etherification with glycidyl trimethylammonium chloride (GTMAC) and (2,3-epoxypropoxy) dodecyldimethylammonium chloride (EDC). The composition of HDCC was characterized by FTIR and ¹H NMR analysis. An improved water solubility and a relatively wide pH buffering path can be achieved for HDCC. With increasing substitution degree of long chain alkyl groups (DS_A) of HDCC hydrogels, the modulus and crosslinking density increased, while the swelling ratios decreased, suggesting the formation of a more compact structure due to the physical entanglement of the long alkyl chains. The encapsulation efficiency (EE) and drug loading capacity (LC) of HDCC hydrogels increased with increasing DS_A, suggesting the enhancement of interactions between the long alkyl chains and bovine serum albumin (BSA). By increasing the pH value from 6.8 to 7.4, a considerable decrease in cumulative release was observed for all hydrogels because the acidic environment could promote the hydrolysis of their cationic groups. Introduction of long alkyl chains slowed down the initial burst release rate of the hydrogels and better pH and glucose sensitive release behavior of BSA and insulin can be observed. Drug release kinetic data under different pH values and glucose concentrations for BSA-loaded hydrogels presented an almost Fickian release behavior, and the kinetic constant k decreased with increasing DS_A, indicating that HDCC hydrogels may achieve a better slow-release effect.