中文摘要：

药物递送系统是克服肿瘤多药耐药性（MDR）的一种新策略。本文以聚合物胶束系统和难溶性药物紫杉醇（PTX）为研究对象，旨在制备一种新型的PTX给药系统，既能增溶难溶性药物，又具有克服肿瘤MDR的能力。以Pluronic P105为载体，采用固体分散-水化法制备PTX聚合物胶束，并以星点设计-效应面优化法进行处方优化。对其粒径、体外释放等性质进行表征后，以人耐药卵巢癌细胞SKOV-3/PTX为细胞模型，体外评价PTX聚合物胶束的细胞摄取及其逆转肿瘤细胞耐药性的作用。结果显示，聚合物胶束制剂的载药量约为1.1%、药物浓度约为700μg·mL^-1、平均粒径约为24 nm。胶束制剂与普通制剂（Taxol）在6 h内的累积释放分别为45.4%和95.2%，前者具有较强的缓释作用；胶束制剂与Taxol对SKOV-3/PTX的IC50值分别为1.14和5.11μg·mL^-1，二者的耐药逆转指数（RRI）分别为9.65和2.15。胶束制剂可促进耐药细胞对P-糖蛋白（P-gp）底物（PTX或Rhodamine-123）的摄取。结果表明，Pluronic P105可有效增溶难溶性药物PTX，并形成具有较强缓释作用的纳米级聚合物胶束制剂，该制剂可显著提高PTX对人卵巢癌耐药细胞的细胞毒性，能逆转其耐药性。

英文摘要：

Drug delivery system （DDS） is a novel approach to overcome muhidrug resistance （MDR） in tumors nowadays. This work was designed to investigate a new micellar delivery system for in vitro reversal of resistant ovarian tumor cells, based on a nonionic triblock copolymer Pluronic P105 and paclitaxel （PTX）. The PTX-loaded polymeric micelles （P105/PTX） were prepared by thin film-hydration methods. Based on the results of single factor experiments, the P105/PTX micelle formulation was optimized by employing the central composite design-response surface methodology. The physico-chemical properties of the P105/PTX micelles were characterized, including micelle size, drug loading coefficient, in vitro release behavior, etc. The cytotoxicity of the P105/PTX micelles was assessed against human ovarian tumor cell line, SKOV-3/PTX, by a standard 3-（4,5-dimethylthiazol-2-yl） -2,5-diphenyl （MTT） assay. In order to understand the possible mechanism of Pluronic effects in resistant tumor cells, cellular uptake study of micellar PTX or Rhodamine-123 （R-123） was also carried out. The results showed that the micelle size was about 24 nm with drug loading coefficient of 1.1% and PTX concentration of 700 μg·mL^-1. The cumulative release amount of PTX from the P105/PTX micelles was only 45.4% in 6 h （P 〈 0.05） and 79.6% in 24 h, whereas Taxol injection in 6 h released 95.2% PTX. The IC50 values of the P105/PTX micelles and Taxol injection against SKOV-3/PTX were 1. 14 and 5. 11 μg·mL^-1, and resistance reversion index （RRI） was 9.65 and 2. 15, respectively. The micellar PTX or R-123 exhibited a significant increase in cellular uptake in resistant SKOV-3/PTX cells compared with free PTX or R-123. These results indicated that PTX could effectively be solubilized by Pluronic P105 block copolymers via thin film-hydration process and formulation optimization, producing nano-scale polymeric micelles with sustained release property in vitro. The P105/PTX micelles were effectively able to reverse resis