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H₂O₂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H₂O₂存在的情况下释药速度加快，在12 h内累积释放量达到53%，48 h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，MRT_0~∞）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 H₂O₂was 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 Cur-loaded 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 H₂O₂, 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 anti-inflammatory 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 (MRT_0-∞) 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.

陕西省中医药管理局科研项目（2021-ZZ-ZY001）