卵巢癌是女性生殖系统恶性肿瘤中死亡率最高、生存率最低的癌症。有手术和化疗的治疗选择，但两者都很有限。在这项研究中，我们开发并评估了由 D-α-生育酚聚乙二醇 (PEG) 1000 琥珀酸酯 (TPGS) 和负载奥拉帕尼 (OLA)（一种聚（ADP-核糖）聚合酶 (PARP) 的 Soluplus® (SOL) 组成的胶束。 ）抑制剂和雷帕霉素（RAPA），雷帕霉素（mTOR）抑制剂在卵巢癌中的哺乳动物靶标。我们制备了含有不同摩尔比的OLA和RAPA的胶束，嵌入不同重量比的TPGS和SOL（OLA/RAPA-TPGS/SOL） ）进行制备并进行物理化学表征。此外，我们还进行了 OLA、RAPA 和 OLA/RAPA-TPGS/SOL 的体外细胞毒性实验。还进行了体内毒性和抗肿瘤功效测定，以评估混合胶束系统的功效。含有 4:1 TPGS:SOL 重量比和 2:3 OLA:RAPA 摩尔比的 OLA/RAPA-TPGS/SOL 显示出协同效应并进行了优化。该制剂的药物包封率>65%，理化性质持续180天。此外，该制剂具有高细胞摄取率并显着抑制细胞迁移（**p < 0.01）。体内毒性试验中，除高剂量组外，未观察到毒性。此外，OLA/RAPA-TPGS/SOL在体内显着抑制肿瘤球体和肿瘤生长。与对照相比，OLA/RAPA-TPGS/SOL表现出显着的肿瘤抑制作用。这些发现为使用负载 OLA 和 RAPA 的 TPGS/SOL 混合胶束治疗卵巢癌奠定了基础。© 2024 Shin 等人。

Ovarian cancer has the highest mortality rate and lowest survival rate among female reproductive system malignancies. There are treatment options of surgery and chemotherapy, but both are limited. In this study, we developed and evaluated micelles composed of D-α-tocopheryl polyethylene-glycol (PEG) 1000 succinate (TPGS) and Soluplus® (SOL) loaded with olaparib (OLA), a poly(ADP-ribose)polymerase (PARP) inhibitor, and rapamycin (RAPA), a mammalian target of rapamycin (mTOR) inhibitor in ovarian cancer.We prepared micelles containing different molar ratios of OLA and RAPA embedded in different weight ratios of TPGS and SOL (OLA/RAPA-TPGS/SOL) were prepared and physicochemical characterized. Furthermore, we performed in vitro cytotoxicity experiments of OLA, RAPA, and OLA/RAPA-TPGS/SOL. In vivo toxicity and antitumor efficacy assays were also performed to assess the efficacy of the mixed micellar system.OLA/RAPA-TPGS/SOL containing a 4:1 TPGS:SOL weight ratio and a 2:3 OLA:RAPA molar ratio showed synergistic effects and were optimized. The drug encapsulation efficiency of this formulation was >65%, and the physicochemical properties were sustained for 180 days. Moreover, the formulation had a high cell uptake rate and significantly inhibited cell migration (**p < 0.01). In the in vivo toxicity test, no toxicity was observed, with the exception of the high dose group. Furthermore, OLA/RAPA-TPGS/SOL markedly inhibited tumor spheroid and tumor growth in vivo.Compared to the control, OLA/RAPA-TPGS/SOL showed significant tumor inhibition. These findings lay a foundation for the use of TPGS/SOL mixed micelles loaded with OLA and RAPA in the treatment of ovarian cancer.© 2024 Shin et al.