包载多西他赛的聚合物胶束抑制小鼠乳腺癌转移作用研究

目的 考察包载多西他赛的聚合物胶束抑制小鼠乳腺癌转移效果。方法 采用薄膜分散法制备两种包载多西他赛（docetaxel，DTX）的聚合物胶束：普通胶束（DSPE-mPEG₂₀₀₀-Micelles，DM）和含聚乙二醇维生素E琥珀酸酯（D-α-tocopheryl polyethylene glycol 1000 succinate，TPGS₁₀₀₀）的聚合物胶束（TPGS₁₀₀₀/DSPE-mPEG₂₀₀₀-Micelles，TDM）。评价胶束包封率、载药量、粒径和zeta电位。采用尾静脉注射4T1/Luc细胞建立小鼠肺转移模型，评价胶束治疗后的肺部肿瘤生物发光强度和结节数量。结果 所制备的载多西他赛聚合物胶束包封率>85%，载药量约为3%，粒径约为20 nm，zeta电位约为 -4 mV，且TDM包封率和载药量更高，粒径更小。两种聚合物胶束均可降低乳腺癌肺转移模型小鼠肺部肿瘤生物发光强度、减少肺部结节数量，且TDM作用更强。结论 含TPGS₁₀₀₀的包载多西他赛的聚合物胶束TDM具有较好的抑制小鼠乳腺癌转移的作用。

Evaluation of the inhibitory effect of docetaxel-loaded polymeric micelles on breast cancer metastasis in mice

Objective To investigate the inhibitory effect of docetaxel-loaded polymeric micelles on breast cancer metastasis in mice. Methods Two kinds of polymer micelles, DSPE-mPEG₂₀₀₀-Micelles (DM) and D-α-tocopheryl polyethylene glycol 1 000 succinate (TPGS₁₀₀₀)/DSPE-mPEG₂₀₀₀-Micelles (TDM), loading with docetaxel (DTX), were prepared by film formation method. The encapsulation, drug loading, size and zeta potential of micelles were evaluated. A mouse lung metastasis model was established by injecting 4T1/Luc cells into the tail vein. The bioluminescence intensity and nodule number of lung tissues after treatment were evaluated. Results The encapsulation rates of prepared polymeric micelles were more than 85% and the drug loading efficiencies were about 3%. The particle sizes were about 20 nm, and the zeta potentials were about -4 mV. The polymeric micelles containing TPGS₁₀₀₀ were characterized with a higher encapsulation rate and drug loading efficiency, and a smaller particle size. Both DM and TDM groups could reduce the bioluminescence intensity of lung tumors and the number of pulmonary nodules in mice with breast cancer lung metastasis model, whilst TDM showed a stronger effect. Conclusion Docetaxel-loaded polymeric micelles containing TPGS₁₀₀₀ exhibited a stronger inhibitory effect on breast cancer metastasis in mice.