Recent advances in chitosan-based smart hydrogel for drug delivery systems.

Achieving sustainable and controllable drug delivery is a highly effective disease treatment approach. Chitosan hydrogels, with their unique three-dimensional (3D) porous structures, offer tunable capacity, controllable degradation, various stimuli sensitivities, and the ability to encapsulate therapeutic agents. These characteristics provide chitosan hydrogels with inherent advantages as vehicles for drug delivery systems. In recent years, there has been a notable shift toward embracing the "back-to-nature" ethos, with biomass materials emerging as promising candidates for constructing chitosan hydrogels used in controlled drug release applications. This trend is sustained by their biodegradability, biocompatibility, and non-toxic properties, emphasizing their unique benefits and innovative features. These hydrogels exhibit sensitivity to various factors such as temperature, pH, ion concentration, light, magnetic fields, redox, ultrasound, and multi-responsiveness, offering opportunities for finely tuned drug release mechanisms. This review comprehensively outlines fabrication methods, properties, and biocompatibility of chitosan hydrogel, as well as modification strategies and stimuli-responsive mechanisms. Furthermore, their potential applications in subcutaneous (wound dressing), parental (transdermal drug delivery), oral (gastrointestinal tract), and facial (ophthalmic and brain) drug delivery are briefly discussed. The challenges in clinical application and the future outlook of chitosan-based smart hydrogel are also highlighted.