Inflammatory bowel diseases(IBD)are the incurable chronic recurrent gastrointestinal disorders and currently lack in safe and effective drugs.In this study,patchouli alcohol,a main active compound of traditional Chine...Inflammatory bowel diseases(IBD)are the incurable chronic recurrent gastrointestinal disorders and currently lack in safe and effective drugs.In this study,patchouli alcohol,a main active compound of traditional Chinese herb patchouli,was developed into biomimetic liposomes for macrophagetargeting delivery for IBD treatment.The developed lactoferrin-modified liposomes(LF-lipo)can specifically bind to LRP-1 expressed on the activated colonic macrophages and achieve cell-targeting anti-inflammatory therapy.LF-lipo reduced the levels of inflammatory cytokines and ROS and suppressed the MAPK/NF-κB pathway.LF-lipo also suppressed the formation of NLRP3 inflammasome and the consequent IL-1βactivation.LF-lipo showed improved therapeutic efficacy in a DSS-induced colitis murine model,evidenced by the reduced disease activity index,the improved colon functions,and the downregulated inflammatory cytokines in the colon.LF-lipo provided an effective and safe macrophagetargeting delivery and therapeutic strategy for addressing the unmet medical need in IBD management.展开更多
基金the financial support of National Natural Science Foundation of China(Nos.81925035,81673382 and 81521005)the Strategic Priority Research Program of Chinese Academy of Sciences(XDA12050307,China)+2 种基金National Special Project for Significant New Drugs Development(2018ZX09711002-010-002,China)Shanghai Sci Tech Innovation Initiative(19431903100 and 18430740800,China)the Fudan-SIMM Joint Research Fund(FU-SIMM20174009,China)for the support
文摘Inflammatory bowel diseases(IBD)are the incurable chronic recurrent gastrointestinal disorders and currently lack in safe and effective drugs.In this study,patchouli alcohol,a main active compound of traditional Chinese herb patchouli,was developed into biomimetic liposomes for macrophagetargeting delivery for IBD treatment.The developed lactoferrin-modified liposomes(LF-lipo)can specifically bind to LRP-1 expressed on the activated colonic macrophages and achieve cell-targeting anti-inflammatory therapy.LF-lipo reduced the levels of inflammatory cytokines and ROS and suppressed the MAPK/NF-κB pathway.LF-lipo also suppressed the formation of NLRP3 inflammasome and the consequent IL-1βactivation.LF-lipo showed improved therapeutic efficacy in a DSS-induced colitis murine model,evidenced by the reduced disease activity index,the improved colon functions,and the downregulated inflammatory cytokines in the colon.LF-lipo provided an effective and safe macrophagetargeting delivery and therapeutic strategy for addressing the unmet medical need in IBD management.
