包载姜黄素的白及多糖载药胶束的活性氧响应性、抗炎作用及肝靶向性研究  

Reactive oxygen species-responsiveness and anti-inflammatory activity of curcumin-loaded Bletilla striata polysaccharide micelles and its liver-targeting

作　　者：王济 党婷婷 赵慧雯 冯斌 WANG Ji;DANG Ting-ting;ZHAO Hui-wen;FENG Bin(State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture,Department of Pharmacy,Hospital of Stomatology,The Fourth Military Medical University,Xi’an 710032,China)

机构地区：[1]军事口腔医学国家重点实验室,国家口腔疾病临床医学研究中心,陕西省口腔生物工程技术研究中心,第四军医大学口腔医院药剂科,陕西西安710032

出　　处：《中草药》2022年第18期5759-5767,共9页Chinese Traditional and Herbal Drugs

基　　金：陕西省中医药管理局科研项目(2021-ZZ-ZY001)。

摘　　要：目的 考察包载模型药物姜黄素(curcumin,Cur)的白及多糖(Bletilla striata polysaccharide,BSP)载药胶束的活性氧(reactive oxygen species,ROS)响应性、抗炎作用以及肝靶向性。方法 采用透析袋法考察Cur载药胶束在HO存在下的体外释放特性;利用荧光显微镜观察Cur载药胶束在富含ROS的巨噬细胞内的响应性释放效果;采用酶联免疫吸附(enzyme linked immunosorbent assay,ELISA)法考察Cur载药胶束的抗炎作用;研究Cur载药胶束在肝纤维化大鼠模型体内的药动学和组织分布情况。结果 Cur载药胶束在HO存在的情况下释药速度加快,在12 h内累积释放量达到53%,48h累积释放量达76%;Cur载药胶束可被富含ROS的巨噬细胞特异性识别并响应性释放药物;Cur与BSP有协同抗炎作用,可协同降低致炎因子的水平;药动学和组织分布研究表明,Cur载药胶束在大鼠体内滞留时间延长,平均滞留时间(mean residence time,MRT0)达(12.109±3.528)h,且在肝脏中分布最多。结论 包载Cur的BSP载药胶束具有ROS响应性、抗炎作用以及肝脏靶向性。Objective To investigate the reactive oxygen species(ROS)-responsiveness, anti-inflammatory activity and liver-targeting properties of Bletilla striata polysaccharide(BSP) micelles loaded with curcumin(Cur). Methods The in vitro release characteristics of drug-loaded micelles in the presence of HOwas investigated by dialysis bag method;The responsive release effect of Cur-loaded micelles in ROS-rich RAW264.7 macrophages was observed by fluorescence microscopy;The anti-inflammatory activities of Curloaded micelles were investigated by enzyme-linked immunosorbent assay(ELISA);The pharmacokinetics and tissue distribution of Cur-loaded micelles in rats with liver fibrosis were also evaluated. Results In the presence of HO, the release rate of Cur-loaded micelles was accelerated, and the cumulative release amount reached 53% within 12 h and 76% within 48 h. The Cur-loaded micelles could be specifically recognized by ROS-rich macrophages and release drugs in response. Cur and BSP had synergistic antiinflammatory effects and could synergistically reduce the levels of inflammatory factors. Pharmacokinetic and tissue distribution studies showed that the retention time of Cur-loaded micelles in rats was prolonged, and the mean residence time(MRT0) was(12.109 ± 3.528) h, and the distribution of Cur-loaded micelles was the most in liver. Conclusion The BSP micelles loaded with Cur have ROS-responsiveness, anti-inflammatory activity and liver-targeting.

关 键 词：白及多糖 姜黄素 活性氧响应 抗炎作用 肝脏靶向 

分 类 号：R283[医药卫生—中药学] R285[医药卫生—中医学]