Thermo-responsive in situ hydrogel enables superior rectal administration and local efficacy of 5-ASA in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract that severely compromises quality of life. First-line therapy with 5-aminosalicylic acid (5-ASA) is limited by poor aqueous solubility, rapid upper gastrointestinal absorption and suboptimal colonic bioavailability. Although rectal administration targets the inflamed mucosa directly, conventional suppositories and enemas often reduce adherence due to discomfort and low acceptability. A thermo-sensitive in situ gelling hydrogel based on poloxamer 407 (P407) is designed to address these limitations. Exploiting its amphiphilic architecture and reversible sol–gel transition at physiological temperature, P407 enables efficient encapsulation of 5-ASA, enhances mucosal adhesion and sustains local drug release. The optimized formulation demonstrates an ideal gelation profile, high muco-adhesive strength, suitable mechanical resistance, excellent injectability and spreadability, preserving the antioxidant properties of 5-ASA. The drug release profile was prolonged, even under acidic pH conditions. In an inflamed intestinal co-culture model, P407-5-ASA hydrogels markedly reduce macrophage infiltration and TNF-α secretion. In a dextran sodium sulfate-induced murine colitis model, the formulation achieves higher colonic accumulation, prolonged residence time and significantly enhanced anti-inflammatory efficacy of 5-ASA. These results underscore the potential of P407-based hydrogels as a high-performance, patient-friendly platform for localized treatment of IBD.