Bletilla striata polysaccharide as a form-dictating carrier enhances the local efficacy of low-dose 5-aminosalicylic acid for intestinal mucosal healing.

Current clinical application of 5-aminosalicylic acid (5-ASA) in treating ulcerative colitis (UC) is hindered by therapeutic limitations and potential toxicity. To address this, the study developed a novel localized drug delivery system based on Bletilla striata polysaccharide (BSP) to enhance therapeutic efficacy. A pivotal finding is the self-assembly of 5-ASA into a dendritic crystalline network within BSP matrix, a unique superstructure identified as crucial for amplifying the local therapeutic action. Among various formulated dosage forms, the drug-loaded fibers exhibited favorable mucoadhesion, mechanical strength, and sustained release properties. In vitro assays confirmed that the low-dose composite promotes the proliferation and migration of damaged colon epithelial cells. In vivo, endoscopic implantation of the fiber effectively promoted the healing of moderate-to-severe ulcers. Notably, the implanted fiber integrated into the regenerated mucosa as a supportive scaffold, demonstrating functions beyond conventional drug delivery. Furthermore, network pharmacology analysis identified MMP9 as a key overlapping target, and molecular docking validated a high-affinity binding mode between 5-ASA and MMP9 (Vina Score: -6.3 kcal/mol). Collectively, this study elucidates a new strategy that leverages the maintenance of a drug's active physical form to promote mucosal repair.