Stimuli-responsive chitosan-based injectable hydrogel for "on-demand" drug release

Compared with traditional drug delivery systems, stimuli-responsive injectable hydrogels exhibit sol-gel transition in response to external stimuli, thus showing significant advantages in the on-demand release of drug molecules. Among them, chitosan-based stimuli-responsive injectable hydrogels have attracted considerable attention due to their excellent biocompatibility. However, the complex components, complicated preparation processes, and toxic chemical crosslinking agents make translating chitosan-based stimuli-responsive injectable hydrogels into clinical applications difficult. In this work, a facile and one-step method was developed to fabricate a stimuli-responsive chitosan-based injectable hydrogel based on the dynamic Schiff's base reaction. The hydrogel exhibited excellent stimuli-responsive properties and thixotropic features, including pH-responsive, self-healable, and injectable properties. Bovine serum albumin (BSA) and fluorescein isothiocyanate-dextran (FITC-dextran) were used as drug models to evaluate the on-demand release profiles of the hydrogel in different pH environments. The increased acidity triggers the release of both BSA and FITC-dextran from the hydrogel. No obvious cytotoxicity of the hydrogel extract was observed from Live/dead and alamarBlue assays on HEK 293 cells. The stimuli-responsive chitosan-based injectable hydrogel system is a promising candidate for on-demand drug release in response to pH stimuli. In this study, we developed a simplified one-step method for crafting a pH-responsive chitosan-based injectable hydrogel using dynamic Schiff's base chemistry.