Sun Ying, Duan Bingchao, Chen Huanhuan, Xu Xiaojuan
College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, China.
Adv Healthc Mater. 2020 Mar;9(6):e1901805. doi: 10.1002/adhm.201901805. Epub 2020 Feb 24.
Therapy of inflammatory bowel disease (IBD) has been a difficult task in the medical field. There is a great clinical need for more effective treatments for IBD. Herein, a targeted oral delivery system of yeast glucan particles (YGPs) carrying a clinically used anti-inflammatory drug methotrexate (MTX) to the inflamed sites in IBD mice for therapy is reported. In the findings, MTX is effectively loaded into YGPs through re-precipitation followed by gelation reaction of alginate to obtain the composite YGPs/MTX, which are internalized into RAW264.7 macrophage cells through dectin-1 and CR3 receptors. Furthermore, YGPs/MTX can suppress the proliferation of macrophage cells efficiently, leading to down-regulation of pro-inflammatory cytokines induced by lipopolysaccharides. Additionally, YGPs accumulate in the inflammation site of colitis mice, enabling YGPs/MTX to target the inflammatory site, significantly improve the efficacy of MTX, and reduce the cytotoxicity of MTX. Therefore, the YGPs-based drug delivery system provides a new strategy for MTX application in the clinical treatment of IBD.
炎症性肠病（IBD）的治疗一直是医学领域的一项艰巨任务。临床上迫切需要更有效的IBD治疗方法。在此，报道了一种酵母葡聚糖颗粒（YGP）靶向口服给药系统，该系统将临床使用的抗炎药物甲氨蝶呤（MTX）输送到IBD小鼠的炎症部位进行治疗。研究结果表明，通过再沉淀法将MTX有效负载到YGP中，随后通过海藻酸盐的凝胶化反应获得复合YGP/MTX，其通过dectin-1和CR3受体内化到RAW264.7巨噬细胞中。此外，YGP/MTX可以有效抑制巨噬细胞的增殖，导致脂多糖诱导的促炎细胞因子下调。此外，YGP在结肠炎小鼠的炎症部位积聚，使YGP/MTX能够靶向炎症部位，显著提高MTX的疗效，并降低MTX的细胞毒性。因此，基于YGP的药物递送系统为MTX在IBD临床治疗中的应用提供了一种新策略。
