透明质酸-青蒿琥酯聚合物胶束对脂多糖诱导的炎症巨噬细胞的杀伤作用  

Killing Effect of Hyaluronic Acid-artesunate Polymeric Micelles on Inflammatory Macrophages Induced by Lipopolysaccharide

作　　者：朱溶月 李依凡 刘艳华[1] 杨嘉玉 ZHU Rongyue;LI Yifan;LIU Yanhua;YANG Jiayu(School of Pharmacy,Ningxia Medical University,Yinchuan 750004)

机构地区：[1]宁夏医科大学药学院,宁夏银川750004

出　　处：《中国医药工业杂志》2023年第7期1075-1081,共7页Chinese Journal of Pharmaceuticals

基　　金：宁夏自然科学基金项目(2023AAC03173)。

摘　　要：以己二酸二酰肼(ADH)为连接臂,制备透明质酸-青蒿琥酯(HA-ADH-1),再采用超声分散法制成聚合物胶束,对其体外表征和体内外抗炎作用进行考察。透射电镜和动态光散射研究表明,HA-ADH-1胶束呈类球形,平均粒径为170.90 nm。HA-ADH-1胶束中的1在pH 7.4的生理环境中48 h累积释放率小于50%,远低于游离1组,证明HAADH-1胶束具有缓释特性,且结构稳定。细胞毒性和摄取试验结果显示,HA-ADH-1胶束依靠结合巨噬细胞表面高表达的CD44受体,可特异性靶向脂多糖诱导的炎症巨噬细胞,增加1在细胞内的蓄积量,因此对炎症巨噬细胞有较好的杀伤效果。Using adipic acid dihydrazide(ADH)as a linkage,the polymer hyaluronic acid(HA)-ADHartesunate(1)was synthesized.Then,the polymeric micelles of HA-ADH-1 were prepared by ultrasonic dispersion.Their characteristics in vitro and anti-inflammatory effects in vitro and in vivo were investigated.The observation of transmission electron microscopy revealed that the HA-ADH-1 micelles was spherical,and the results of dynamic light scattering showed that the average particle size of HA-ADH-1 micelles was 170.90 nm.The cumulative release at 48 h of 1 from HA-ADH-1 micelles in the physiological environment(pH 7.4)was less than 50%,which was much lower than that of free 1,indicating that HA-ADH-1 micelles had sustained-release property and stable structure.The cytotoxicity and uptake assay results showed that HA-ADH-1 micelles could bind to CD44 receptors highly expressed on the macrophage surface,showing specific targeting to inflammatory macrophages induced by lipopolysaccharide,then enhanced the intracellular accumulation of 1.Therefore,the micelles demonstrated a better killing effect on inflammatory macrophages.

关 键 词：青蒿琥酯 透明质酸 聚合物胶束 巨噬细胞 抗炎 

分 类 号：R944.9[医药卫生—药剂学]