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聚乙二醇1000维生素E琥珀酸酯-米托蒽醌前药胶束的制备及其抗肿瘤活性

高雅晗, 平其能, 宗莉

高雅晗, 平其能, 宗莉. 聚乙二醇1000维生素E琥珀酸酯-米托蒽醌前药胶束的制备及其抗肿瘤活性[J]. 中国药科大学学报, 2016, 47(3): 311-316. DOI: 10.11665/j.issn.1000-5048.20160311
引用本文: 高雅晗, 平其能, 宗莉. 聚乙二醇1000维生素E琥珀酸酯-米托蒽醌前药胶束的制备及其抗肿瘤活性[J]. 中国药科大学学报, 2016, 47(3): 311-316. DOI: 10.11665/j.issn.1000-5048.20160311
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GAO Yahan, PING Qineng, ZONG Li. Preparation and antitumor activity of mitoxantrone conjugated D-α-tocopherylpolyethylene glycol 1000 succinate prodrug micelle[J]. Journal of China Pharmaceutical University, 2016, 47(3): 311-316. DOI: 10.11665/j.issn.1000-5048.20160311
Citation: GAO Yahan, PING Qineng, ZONG Li. Preparation and antitumor activity of mitoxantrone conjugated D-α-tocopherylpolyethylene glycol 1000 succinate prodrug micelle[J]. Journal of China Pharmaceutical University, 2016, 47(3): 311-316. DOI: 10.11665/j.issn.1000-5048.20160311
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聚乙二醇1000维生素E琥珀酸酯-米托蒽醌前药胶束的制备及其抗肿瘤活性

  • 1.

    中国药科大学天然药物活性组分与药效国家重点实验室

  • 2.

    药剂学教研室

基金项目: 国家自然科学基金资助项目(No.81273467)

Preparation and antitumor activity of mitoxantrone conjugated D-α-tocopherylpolyethylene glycol 1000 succinate prodrug micelle

摘要

    摘要
  • 摘要: 为了提高化疗药物的抗肿瘤疗效，将米托蒽醌(MTO)与聚乙二醇1000维生素E琥珀酸酯(TPGS)通过丁二酸连接臂化学键合形成前体药物(TPGS-MTO)。该前药在水中能够自组装形成胶束，HPLC测定MTO的载药量为(18.61±0.24)%；粒径电位仪测得的胶束粒径为(25.61±0.92)nm，多分散指数PDI为0.22±0.04，Zeta电位为-(3.98±0.09)mV；透射电镜(TEM)显示胶束为均匀的类球形结构；体外生理环境下24 h内粒径无明显变化；体外研究显示胶束在生理条件下无突释现象，24 h释放量为9.04%，随着pH降低，释放速率加快；细胞摄取实验表明，TPGS-MTO胶束可有效促进MCF-7细胞对药物的摄取，6 h的摄取量较MTO溶液提高1.18倍。MTT法结果显示，胶束对乳腺癌细胞MCF-7和MCF-7/MDR均具有明显的抗肿瘤作用，尤其对耐药株细胞，TPGS-MTO表现出优于MTO的抑制效果。TPGS-MTO有望开发为一种水溶性抗肿瘤前药制剂，提高其抗肿瘤活性。
    Abstract: To improve the theraputic effect of chemotherapeutic drugs, D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)was employed as a carrier of mitoxantrone(MTO). MTO was successfully conjugated to TPGS via succinic anhydride to prepare TPGS-MTO prodrug. The prodrug was then self-assembled into TPGS-MTO micelle, with the particle size of(25. 61±0. 92)nm, the polydispersity of 0. 22±0. 04 and the Zeta potential of -(3. 98±0. 09)mV. The micelle was homogeneous spheres under the observation of transmission electron microscope(TEM). The drug loading capacity(DLC)was(18. 61±0. 24)% by HPLC. Meanwhile, the particle size of TPGS-MTO micelle remained stable in 24 h. TPGS-MTO showed a controlled drug release profile with only 9. 04% MTO being detected in 24 h in neutral conditions, and faster release was achieved by decreasing pH in media. Cellular uptake experiments showed that micelle was 1. 18 times more effective than parent drug after 6 h incubation on MCF-7 cells. The cytotoxicity of micelle on MCF-7 and MCF-7/MDR cells was detected by MTT, both with anti-tumor activity, especially on MCF-7/MDR cells. In conclusion, TPGS-MTO prodrug micelle could be a potential formulation of higher therapeutic effects and fewer side-effects than MTO itself.
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    • 参考文献(15)
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  • 刊出日期:  2016-06-24

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