Cancer is a kind of malignant diseases that threatens human health and the research application of anti-tumor drug therapeutics is growingly always been focused on. Many new compounds with great anticancer activity were synthesized but cannot be hard to be developed into clinical use due to its poor water solubility. Deoxypodophyllotoxin (DPT) is just an example. We develop lyophilized Deoxypodophyllotoxin (DPT) loaded polymeric micelles using methoxy polyethylene glycol-block-Poly (D, L-lactide) (mPEG-PLA). DPT-PM freeze-dried powder was successfully prepared using optimized formulation. mPEG-PLA was added to hydration media before hydrating as cryoprotectants. The freeze-dried powder exhibited white pie-solid without collapsing, and the particle size of DPT-PM reconstituted with water was about 20-35 nm. The entrapment efficiency of the reconstituted solution was 98%, which shows no differences with the micelles before lyophilization. In-vitro cytotoxicity and cellular uptake studies showed that DPT-PM has a higher degree of cytotoxicity comparing with DPT and mPEG-PLA micelles and uptake of mPEG-PLA was concentration and time-dependent. In vivo characterization of DPT-PM was done for pharmacokinetics behaviors, antitumor activity and safety. The obtained results showed significant improvement in plasma clearance bioavailability (p <0.05) and prolonged blood circulation time comparing with DPT-HP-β-CD. Moreover, mPEG-PLA micelles had a better degree of anti-tumor efficacy, this was due to better accumulation of mPEG-PLA in tumor cell via enhanced permeability and retention (EPR) effect. Therefore, DPT-PM has great clinical value, and can be expected to be a novel antitumor preparation.

中文翻译：

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高负载的脱氧鬼臼毒素纳米制剂由甲氧基聚乙二醇嵌段聚（D，L-丙交酯）胶束提供，可用于有效的癌症治疗。

癌症是威胁人类健康的一种恶性疾病，抗肿瘤药物疗法的研究应用日益受到关注。合成了许多具有很强抗癌活性的新化合物，但由于其水溶性差，因此很难被开发用于临床。脱氧鬼臼毒素（DPT）只是一个例子。我们开发了使用甲氧基聚乙二醇嵌段聚（D，L-丙交酯）（mPEG-PLA）冻干的脱氧鬼臼毒素（DPT）负载的聚合物胶束。使用优化配方成功制备了DPT-PM冻干粉。在水合作用之前，将mPEG-PLA添加到水合作用介质中作为冷冻保护剂。冷冻干燥的粉末显示出白色的饼状固体而不塌陷，并且用水重构的DPT-PM的粒径为约20-35nm。重构溶液的包封率为98％，与冻干前的胶束无差异。体外细胞毒性和细胞吸收研究表明，与DPT和mPEG-PLA胶束相比，DPT-PM具有更高的细胞毒性，并且mPEG-PLA的吸收呈浓度和时间依赖性。DPT-PM的体内表征用于药代动力学行为，抗肿瘤活性和安全性。与DPT-HP-β-CD相比，所获得的结果显示血浆清除生物利用度显着提高（p <0.05），血液循环时间延长。此外，mPEG-PLA胶束具有更好的抗肿瘤功效，这是由于mPEG-PLA通过增强的通透性和保留（EPR）效应在肿瘤细胞中更好的积累。因此，DPT-PM具有很大的临床价值，