Recent progress in stimuli-responsive hydrogel-based drug delivery for inflammatory bowel disease

Inflammatory bowel disease is a chronic and recurrent inflammatory disorder of the gastrointestinal tract, with its incidence continuously increasing worldwide. Currently available clinical therapeutic drugs generally suffer from limitations including poor targeting efficiency, insufficient local drug concentration at lesion sites, and significant toxic side effects, making them inadequate to meet the growing demand for precision therapy. Stimuli-responsive hydrogels, as intelligent delivery carriers, can recognize abnormal signals within the microenvironment of inflammatory bowel disease lesions, such as pH, temperature, reactive oxygen species, and specific enzymes, and undergo swelling, degradation, or phase transition from sol to gel, thereby enabling spatiotemporally controlled drug release and providing new avenues for the precise treatment of inflammatory bowel disease. This review systematically summarizes the response mechanisms and respective advantages of four types of hydrogels based on pH, temperature, reactive oxygen species, and enzyme responsiveness, and further discusses the processing characteristics and key advantages of emulsion methods, electrospray encapsulation, and droplet microfluidics for hydrogel fabrication. Subsequently, the critical roles of these hydrogels in restoring intestinal homeostasis through multiple synergistic mechanisms, including repair of the intestinal mucosal barrier, elimination of excessive reactive oxygen species, regulation of the gut microbiota, and remodeling of the immune microenvironment, are highlighted. Finally, this review discusses the challenges faced by stimuli-responsive hydrogels in clinical translation and provides perspectives on future development directions, including multi-responsive integrated systems, intelligent delivery platforms, and personalized therapy, aiming to provide new insights and strategies for the precision treatment of inflammatory bowel disease.