Abstract

Although berberine has notable anti-inflammatory and antioxidant effects for ulcerative colitis (UC) treatment, its clinical application is limited by poor oral bioavailability. To improve berberine delivery, we developed colon-targeted mucoadhesive Eudragit® S100/Bletilla striata polysaccharide (EB)-coated microspheres (MPs) encapsulating berberine hydrochloride (BH)–hydrogenated soy phosphatidylcholine (HSPC) complex. BSP acts as both a bioadhesive carrier for prolonged mucosal retention and an immunoregulatory agent synergizing with berberine. Fabricated via electrospray and fluidised-bed coating, the formulation realized pH-responsive colon-specific release. In vitro studies, it showed favorable pH-dependent release, scavenged reactive oxygen species, and promoted M2 macrophage polarization. Small animal fluorescence imaging studies have confirmed its colon-targeting and mucoadhesive properties. In DSS-induced acute and FXY-DSS-induced chronic colitis models, EB@BH–HSPC significantly alleviated inflammation, restored intestinal barrier function, and reduced oxidative stress, with improved therapeutic effects attributed to berberine-BSP synergy and integrated delivery advantages. BSP serves as both film-forming adhesive component and synergistic therapeutic component, making this system a potent strategy for UC treatment.