Mucoadhesive and pH-Responsive Berberine-Bletilla Striata Polysaccharide Core-Shell Microspheres for Colon-Targeted Synergistic Therapy of Ulcerative Colitis

Although berberine possesses notable anti-inflammatory and antioxidant properties for ulcerative colitis (UC) treatment, its clinical utility is limited by poor oral bioavailability. To enhance berberine delivery, we engineered Eudragit® S100/Bletilla striata polysaccharide(EB)-coated berberine hydrochloride (BH)- hydrogenated soy phosphatidylcholine complex(HSPC) microspheres(MPs) a colon-targeted mucoadhesive micro‑nanocomposite. This system encapsulates a solubility-enhanced berberine‑phospholipid complex within microspheres coated with Eudragit® S100 and Bletilla striata polysaccharide (BSP). BSP serves a dual role as a bioadhesive carrier for prolonged mucosal retention and an immunoregulatory agent that synergizes with berberine. Utilizing electrospray and fluidized‑bed coating, the formulation achieved pH‑responsive, colon‑specific release. In vitro, the formulation exhibited favorable pH-dependent controlled release behavior, effectively scavenged reactive oxygen species, and promoted macrophage polarization towards the anti-inflammatory M2 phenotype. In DSS-induced acute and FXY-DSS-induced Spleen Deficiency chronic colitis models, EB@BH-HSPC significantly alleviated inflammation, restored intestinal barrier function, and attenuated oxidative stress, achieving improved therapeutic outcomes. It could be attributed to the synergy of berberine and BSP, combined with the integrated delivery advantages of improved solubility, precise colon targeting, and extended mucosal retention. In this system, BSP functions not only as an excipient but also as a synergistic therapeutic component with berberine. With its colon-targeting and mucoadhesive properties, the system provides a potent and integrated strategy for the treatment of ulcerative colitis.