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

• Published in: Phytomedicine (Stuttgart) 2020-11, Vol.78, p.153293, Article 153293
• Main Authors: Wang, Dan, Sun, Minghui, Zhang, Ying, Chen, Zehong, Zang, Shuya, Li, Genyun, Li, Gao, Clark, Andrew R., Huang, Jiangeng, Si, Luqin
• Format: Article
• Language: English
• Subjects: Colon-targeted delivery; Emodin; Mucosa repair; Nanoparticles; Toxicity; Ulcerative colitis
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2020.153293

•A multifunctional nanosystem (EMO/PSM NPs) could enhance the targeted efficacy on UC by pH-dependent release and nano-adhesive retention.•EMO/PSM NPs could effectively circumvent the liver injury caused by free emodin under an inflammatory state.•Emodin facilitating the reconstruction of the intestinal mucosa barrier was first proposed and demonstrated associated with serum zonulin-related tight junctions and MUC2. 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. 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. 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. EMO/PSM NPs with a desirable hydrodynamic diameter (~ 235 nm) and negative zeta potential (~ -31 mV) could prevent the premature drug release (< 4% in the first 6 h in vitro) in the upper gastrointestinal tract (GIT) and boost retention in the lower GIT and inflamed colon mucosa in vivo. Compared to free EMO-treatment of different doses in UC mice, the NPs could enhance the remedial efficacy of EMO in DAI decline, histological remission, and regulation of colitis indicators, such as myeloperoxidase (MPO), nitric oxide (NO), and glutathione (GSH). The inflammatory factors including induced nitric oxide synthase (iNOS), cyclooxygenase-2