Hesperidin-loaded Eudragit S100 nanoparticles alleviate ulcerative colitis by repairing intestinal barrier and modulating gut microbiota

作者：Jiazheng Zhou, Min Liu, Monong Su, Xingxuan Zhou, Yan Yang, Yuxin Wang, Xiaohan Li, Jingyu Wang, Liang Wang, George Zhang · 发表于：International Journal of Pharmaceutics X · 年份：2026 · DOI：10.1016/j.ijpx.2026.100524 · 被引用次数：1 · 研究领域：Inflammatory Bowel Disease、Gut microbiota and health、Barrier Structure and Function Studies

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with no curative therapy. Hesperidin (HDN) exhibits potent anti-inflammatory and antioxidant properties, but its poor solubility limits its therapeutic application. Here, we developed a colon-targeted nano-formulation by encapsulating HDN in pH-responsive Eudragit S100 nanoparticles (HDN-EUD NPs). The nanoparticles were optimized using Box-Behnken Design, yielding uniform spherical morphology with a mean particle size of 174.4 nm and encapsulation efficiency of 83.98%. HDN-EUD NPs remained stable in simulated gastric and intestinal fluids but rapidly disintegrated in simulated colonic fluid, releasing 74% of HDN within 2 h. At the cellular level, HDN-EUD NPs exhibited excellent biocompatibility and significantly enhanced protection against H₂O₂-induced oxidative stress and apoptosis. In vivo biodistribution confirmed prolonged colonic retention of HDN-EUD NPs. In a DSS-induced UC mouse model, HDN-EUD NPs treatment significantly alleviated disease symptoms, as evidenced by attenuated body weight loss, reduced disease activity index (2.06 vs. 3.61), and restored colon length (6.8 cm vs. 4.5 cm) compared to the DSS group. Mechanistically, HDN-EUD NPs repaired the intestinal barrier by upregulating tight junction proteins ZO-1 and Occludin, downregulated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and myeloperoxidase activity (from 3.56 to 1.02 U/g) in colon tissue, and restored gut microbiota balance by increasi...