Preparation of a pH sensitive hydrogel based on dextran and polyhydrazide for release of 5-flurouracil, an anticancer drug

Abstract

A new hydrogel network was designed to study its capability in hydrophilic drug delivery. Two sets of chemically cross-linked hydrogels were prepared under mild conditions with different cross-linking densities. The precursors obtained by modification of a natural polymer and a synthetic polymer. Oxidation of dextran, natural polymer, produced dextran aldehyde (DA) with reactive aldehyde functionalities and aminolysis of polysuccinimide (PSI) resulted in polyhydrazide (PHZ) formation with reactive hydrazide groups. These two polymers reacted via Schiff-base reaction to form hydrozone linkages as cross-linking sites. The resultant gels showed no toxicity towards L929 mouse fibroblast cells. These biocompatible hydrogels were used for encapsulation and release of 5-flurouracil (5-FLU), a hydrophilic anticancer drug. 5-FLU was released in almost two days from high cross-linked matrix through an anomalous diffusion mechanism. Swelling, degradation and mechanical properties of these networks were studied, and it was observed that the cross-linking density can change the characteristics of the gel. Hydrogel with higher cross-linking density showed longer degradation and lower swelling index and stiffer network compared to the system with lower cross-linking density. The degradation and release behaviour of the gels were sensitive to the pH of medium suggesting faster hydrolysis of hydrozone bonds in lower pH environment.