A Novel Strategy for Treating Inflammatory Bowel Disease by Targeting Delivery of Methotrexate through Glucan Particles
Ying Sun, Bingchao Duan, Huanhuan Chen, Xiaojuan Xu
Abstract
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.