A baicalein nanoparticle-embedded mucoadhesive hydrogel for synergistic anti-inflammation therapy in ulcerative colitis.

Natural bioactive compounds exhibit significant antioxidant and anti-inflammatory activities, offering a promising natural alternative or complement to current immunosuppressive therapies for ulcerative colitis (UC). However, achieving effective colon-targeted delivery of these compounds remains a significant challenge due to premature drug release and limited local retention. In this study, we present a nanoparticle-hydrogel composite system, BZH@HCE, designed to enhance the therapeutic efficacy of baicalein (BA) for UC treatment. Zein and oxidized hyaluronic acid-based nanoparticles (BZH) provide a high loading capacity for BA and prevent premature drug release in the upper gastrointestinal tract. BZH encapsulation within an epigallocatechin gallate (EGCG)-containing hydrogel matrix (HCE) further sustains BA release and amplifies its antioxidant and anti-inflammatory effects through synergistic action with EGCG. The adhesive hydrogel matrix ensures prolonged colon retention for up to 24 hours in colitis mice. In vivo studies using a dextran sulfate sodium-induced murine colitis model demonstrate that BZH@HCE significantly alleviates intestinal inflammation, promotes epithelial barrier repair, and shows excellent biocompatibility, outperforming both free BA and BZH nanoparticles. These findings position BZH@HCE as a versatile and effective platform for UC therapy, highlighting its potential as a natural, bioactive compound-based treatment.