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

doi:10.3969/j.issn.1006-7795.2020.02.013

首都医科大学学报 ›› 2020, Vol. 41 ›› Issue (2): 225-230.doi: 10.3969/j.issn.1006-7795.2020.02.013

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

王爱婷^1,2, 鄢丹^1,2, 齐宪荣³

1. 首都医科大学附属北京世纪坛医院药剂科, 北京 100038;
2. 临床合理用药生物特征谱学评价北京市重点实验室, 北京 100038;
3. 北京大学医学部药学院药剂学系, 北京 100191

收稿日期:2019-07-10 出版日期:2020-04-21 发布日期:2020-04-16
通讯作者: 齐宪荣 E-mail:qixr@bjmu.edu.cn
基金资助:
国家"重大新药创制"科技重大专项（2017ZX09301-040），北京市优秀人才培养资助青年骨干个人项目（2017000021469G267）。 This study was supported by National Great New Drugs Development Project of China （2017ZX09301-040）， Beijing Excellent Talents Training Fund （2017000021469G267）.

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

Wang Aiting^1,2, Yan Dan^1,2, Qi Xianrong³

1. Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China;
2. Beijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China;
3. School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2019-07-10 Online:2020-04-21 Published:2020-04-16
Supported by:
This study was supported by National Great New Drugs Development Project of China （2017ZX09301-040）， Beijing Excellent Talents Training Fund （2017000021469G267）.

摘要/Abstract

摘要： 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。

关键词: 多西他赛, 聚乙二醇维生素E琥珀酸酯, 聚合物胶束, 乳腺癌转移

Abstract: 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.

Key words: docetaxel, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS₁₀₀₀), polymeric micelles, breast cancer metastasis

中图分类号:

R943

王爱婷, 鄢丹, 齐宪荣. 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[J]. 首都医科大学学报, 2020, 41(2): 225-230.

Wang Aiting, Yan Dan, Qi Xianrong. Evaluation of the inhibitory effect of docetaxel-loaded polymeric micelles on breast cancer metastasis in mice[J]. Journal of Capital Medical University, 2020, 41(2): 225-230.

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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

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

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