Nedaplatin (NDP) plays an important role in the chemotherapies of non-small cell lung cancer (NSCLC). However, dose-limiting toxicities such as myelosuppression and drug resistance restrict its clinical application. Herein, we intended to overcome these defects by developing a PEGylated liposomal formulation encapsulated NDP (NDP-LPs). For the first time, we found the incompatibility between NDP and natural phospholipids such as egg phosphatidylcholine (EPC) using the high-performance liquid chromatography (HPLC) method. The orthogonal experimental design was applied to optimize the conditions for preparing NDP-LPs, with encapsulation efficiency (EE) as the evaluation indicator. The physicochemical properties of optimized NDP-LPs were further characterized, including particle size, zeta potential, EE, drug release profiles, and so on. Results showed that a significantly sustained-release profile of NDP-LPs was observed and the releasing time of NDP could reach as long as 8 days. At the cellular level, NDP encapsulated in the PEGylated liposomes enhanced its cellular uptake and possessed potent cytotoxic activity. After intravenous injection, NDP-LPs could accumulate at tumor sites and effectivelyinhibit tumor growth of mice without obvious adverse effects. In conclusion, our results demonstrated that PEGylated liposomes could serve as a promising carrier to enhance the therapeutic effects of NDP.

中文翻译：

---

制备具有缓释行为的聚乙二醇化奈达铂脂质体以增强非小细胞肺癌的抗肿瘤疗效


内达铂 （NDP） 在非小细胞肺癌 （NSCLC） 的化疗中起重要作用。然而，骨髓抑制和耐药等剂量限制性毒性限制了其临床应用。在此，我们打算通过开发聚乙二醇化脂质体制剂封装的 NDP （NDP-LPs） 来克服这些缺陷。我们首次使用高效液相色谱 （HPLC） 方法发现了 NDP 与鸡蛋磷脂酰胆碱 （EPC） 等天然磷脂之间的不相容性。采用正交实验设计优化制备 NDP-LPs 的条件，以包埋效率 （EE） 为评价指标。进一步表征了优化的 NDP-LPs 的物理化学性质，包括粒径、zeta 电位、EE、药物释放曲线等。结果表明，观察到 NDP-LPs 的显著缓释曲线，NDP 的释放时间可长达 8 d。在细胞水平上，封装在聚乙二醇化脂质体中的 NDP 增强了其细胞摄取并具有强大的细胞毒活性。静脉注射后，NDP-LPs可在肿瘤部位蓄积，有效抑制小鼠肿瘤生长，无明显不良反应。总之，我们的结果表明，聚乙二醇化脂质体可以作为增强 NDP 治疗效果的有前途的载体。