米非司酮是一种黄体酮受体拮抗剂，最初用于终止早孕。随着科学研究的进展，它可以有效治疗各种肿瘤和肿瘤样疾病，例如子宫内膜异位症。尽管米非司酮具有治疗潜力，但由于药物难以溶解并在靶组织部位积聚，其治疗效果仍远不理想。针对这一问题，通过简单的溶剂扩散法制备了米非司酮纳米结构脂质载体（Mif-NLC），并对其抗子宫内膜异位症的性能和机制进行了初步研究。通过优化制备方案，我们获得了平均粒径为 280 nm 的均匀球形 Mif-NLC。紫外分光光度法测定包封率和载药量分别为64.67%±0.15%和2.7%±0.014%。体外释放动力学表明米非司酮以缓释方式从NLC中释放。与游离米非司酮相比，Mif-NLC 表现出增强的细胞摄取和抑制子宫内膜异位症原代间充质细胞的侵袭活性。与对照组相比，在动物中观察到子宫内膜异位囊肿的大小有一定程度的减小。通过 Mif-NLC 诱导自噬可能是这种效应的分子机制。此外，对子宫结构的观察显示毒性作用可以忽略不计。这表明NLC封装的米非司酮可以提高其生物利用度和抗子宫内膜异位症疗效，为子宫内膜异位症的治疗提供了新策略。©2024。控释协会。

Mifepristone, a progesterone receptor antagonist, was initially used to terminate early pregnancy. As scientific research advanced, it emerged to be effective in the treatment of various tumors and tumor-like conditions such as endometriosis. Despite the therapeutic potential of mifepristone, its therapeutic effect is still far from ideal because the drug is difficult to dissolve and to accumulate in the target tissue sites. To address this issue, mifepristone-loaded nanostructured lipid carriers (Mif-NLC) were prepared by a simple solvent diffusion method and their anti-endometriosis performance and mechanisms were initially investigated. By optimizing the preparation protocol, we obtained uniform and spheroidal Mif-NLC with an average particle size of 280 nm. The encapsulation rate and drug loading capacity were 64.67% ± 0.15% and 2.7% ± 0.014%, respectively, as measured by UV spectrophotometry. The in vitro release kinetics indicated that mifepristone was released from NLC in a sustained-release manner. Compared with free mifepristone, Mif-NLC exhibited enhanced cellular uptake and inhibition of invasion activity in primary mesenchymal cells of endometriosis. A certain reduction in the size of endometriotic cysts was observed in animals compared to controls. The induction of autophagy via Mif-NLC may serve as the molecular mechanism underlying this effect. Furthermore, observation of uterine structures showed negligible toxic effects. This suggested that mifepristone encapsulated in NLC can improve its bioavailability and anti-endometriosis efficacy, which provided a new strategy for the treatment of endometriosis.© 2024. Controlled Release Society.