Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, People's Republic of China.
Nanomedicine. 2012 Aug;8(6):925-34. doi: 10.1016/j.nano.2011.11.005. Epub 2011 Nov 17.
The purpose of this study was to develop polymeric nanoscale drug-delivery system (nano-DDS) for paclitaxel (PTX) from poly(ɛ-caprolactone)-poly(ethylene glycol)-poly(ɛ-caprolactone) (PCL-PEG-PCL, PCEC) copolymers, intended to be intravenously administered, able to improve the therapeutic efficacy of the drug and devoid of the adverse effects of Cremophor EL. Both of the PTX-loaded polymeric micelles and polymersomes were successfully prepared from PCEC copolymers. The obtained PTX-loaded micelles exhibited core-shell morphology with satisfactory size (93 nm), and were favorable for intravenous injection. In vitro cytotoxicity demonstrated that the cytotoxic effect of PTX-loaded micelles was lower than that of Taxol (Bristol-Myers Squibb, Princeton, New Jersey). Pharmacokinetic results indicated that the PTX-loaded micelles had longer systemic circulation time and slower plasma elimination rate than those of Taxol. Furthermore, PTX-loaded micelles showed greater tumor growth-inhibition effect in vivo on EMT6 breast tumor, in comparison with Taxol. Therefore, the prepared polymeric micelles might be potential nano-DDS for PTX delivery in cancer chemotherapy.
本研究旨在开发一种载紫杉醇（PTX）的聚合物纳米给药系统（nano-DDS），所用聚合物为聚（ε-己内酯）-聚乙二醇-聚（ε-己内酯）（PCL-PEG-PCL，PCEC）共聚物，拟通过静脉注射给药，以提高药物的治疗效果并避免 Cremophor EL 的不良反应。负载 PTX 的聚合物胶束和聚合物囊泡均成功地由 PCEC 共聚物制备得到。所得载 PTX 胶束呈核壳形态，具有令人满意的尺寸（93nm），有利于静脉注射。体外细胞毒性实验表明，载 PTX 胶束的细胞毒性低于 Taxol（百时美施贵宝，新泽西州普林斯顿）。药代动力学结果表明，与 Taxol 相比，载 PTX 胶束具有更长的系统循环时间和更慢的血浆消除率。此外，与 Taxol 相比，载 PTX 胶束在 EMT6 乳腺癌动物模型中具有更强的肿瘤生长抑制作用。因此，所制备的聚合物胶束可能是用于癌症化疗中 PTX 递送的有潜力的 nano-DDS。
