Enhanced therapeutic efficacy of a novel colon-specific nanosystem loading emodin on DSS-induced experimental colitis

Abstract Background : Ulcerative colitis (UC) is an intricate enteric disease with a rising incidence that is closely related to mucosa-barrier destruction, gut dysbacteriosis, and immune disorders. Emodin (1,3,8-trihydroxy-6-methyl-9,10-anthraquinone, EMO) is a natural anthraquinone derivative that occurs in many Polygonaceae plants. Its multiple pharmacological effects, including antioxidant, immune-suppressive, and anti-bacteria activities, make it a promising treatment option for UC. However, its poor solubility, extensive absorption, and metabolism in the upper gastrointestinal tract may compromise its anti-colitis effects. Purpose : EMO was loaded in a colon-targeted delivery system using multifunctional biomedical materials and the enhanced anti-colitis effect involving mucosa reconstruction was investigated in this study. Methods : EMO-loaded Poly (DL-lactide-co-glycolide)/Eudragit® S100/montmorillonite nanoparticles (EMO/PSM NPs) were prepared by a versatile single-step assembly approach. The colon-specific release behavior was characterized in vitro and in vivo, and the anti-colitis effect was evaluated in dextran sulfate sodium (DSS)-induced acute colitis in mice by weight loss, disease activity index (DAI) score, colon length, histological changes, and colitis biomarkers. The integrity of the intestinal mucosal barrier was evaluated through transwell co-culture model in vitro and serum zonulin-related tight junctions and mucin2 (MUC2) in vivo. Results : EMO/PSM NPs with a desirable hydrodynamic diameter (∼ 235 nm) and negative zeta potential (∼ -31 mV) could prevent the premature drug release ( Conclusion : Our results demonstrated that EMO/PSM NPs could specifically release EMO in the diseased colon, and effectively enhance the anti-colitis effects of EMO related to intestinal barrier improvement. It can be considered as a novel potential alternative for oral colon-targeted UC therapy by increasing therapeutic efficacy and reducing side-effects.