Abstract：
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.
摘要：
米非司酮,孕激素受体拮抗剂,最初用于终止早期妊娠。随着科学研究的进展，它在治疗各种肿瘤和肿瘤样疾病如子宫内膜异位症方面是有效的。尽管米非司酮具有治疗潜力,由于该药物难以溶解并在靶组织部位积聚，其治疗效果仍远非理想。为了解决这个问题，通过简单的溶剂扩散法制备了负载米非司酮的纳米结构脂质载体（Mif-NLC），并初步研究了它们的抗子宫内膜异位症性能和机制。通过优化制备方案，我们获得了均匀和球形的Nif-NLC，平均粒径为280nm。包封率和载药量分别为64.67%±0.15%和2.7%±0.014%,分别,通过紫外分光光度法测量。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在子宫内膜异位症的原代间充质细胞中表现出增强的细胞摄取和侵袭活性的抑制。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所减少。通过Mif-NLC诱导自噬可能是这种作用的分子机制。此外，对子宫结构的观察显示出可忽略的毒性作用。这表明米非司酮包裹在NLC中可以提高其生物利用度和抗子宫内膜异位症的功效。为子宫内膜异位症的治疗提供了新的策略。
