青蒿素
类风湿性关节炎
前药
材料科学
药物输送
基因传递
药品
药理学
遗传增强
脂质体
体内
阳离子聚合
纳米技术
医学
化学
生物
疟疾
免疫学
生物化学
基因
生物技术
恶性疟原虫
高分子化学
作者
Chao Li,Yawei Du,Hongzhi Lv,Jun Zhang,Pengzhen Zhuang,Yang Wu,Yingze Zhang,Juan Wang,Wenguo Cui,Wei Chen
标识
DOI:10.1002/adfm.202206261
摘要
Abstract Artemisinin and its derivatives (artemisinins) are first‐line chemotherapeutic agents of lethal malaria, which also showed tremendous value in many other diseases including chronic inflammation. Unfortunately, almost all artemisinins are rapid‐acting medicines with an extremely short half‐life in vivo, which significantly limits their clinical application for these new adaptation diseases. In this study, a locally injectable long‐acting gene/artemisinin co‐delivery nano‐microplex consisting of a biodegradable hyaluronic acid (HA) microsphere and releasable gene/artemisinin co‐delivery nano‐lipoplex is developed first, to obtain an improved efficacy for rheumatoid arthritis (RA). Briefly, a cationic multicomponent drug‐embedded liposome with pharmacological activity is first reported based on two novel artemisinin derivatives (dAPC and dACC), which possess mimic phospholipids and cationic lipids, respectively. A cationic artemisinin‐embedded lipoplex is first reported as a medicative gene carrier here. An in situ injectable TNF‐α siRNA/artemisinin co‐delivery nano‐microplex (MTAsi@MG) is further prepared by immobilization of TNF‐α siRNA/lipoplex on porous microfluidic HA microspheres. Using this nano‐microplex for intra‐articular injection, the sustaining activity of gene therapy and artemisinin efficacy for RA long‐term treatment is first realized. Undoubtedly, this intra‐articular injectable TNF‐α siRNA/artemisinin co‐delivery nano‐microplex based on dAPC/dACC lipoplex and microfluidic microspheres would be one of the most potent gene/drug co‐delivery systems for RA therapy.
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