...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>International Journal of Pharmaceutics >Comparison of two kinds of docetaxel-vitamin E prodrugs: In vitro evaluation and in vivo antitumor activity
【24h】

Comparison of two kinds of docetaxel-vitamin E prodrugs: In vitro evaluation and in vivo antitumor activity

机译：两种多西他赛-维生素E前药的比较：体外评估和体内抗肿瘤活性

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

To achieve optimal therapeutic index of docetaxel, we conjugated docetaxel (DTX) with vitamin E (VE) by ester bond with disulfide bond or thioether bond as spacer to produce DTX-ss-VE or DTX-s-VE. The two prodrugs were successfully loaded into liposomes. The physicochemical characterization and in vitro release profiles of the prodrug loaded liposomes were investigated. MIT assays showed that the cytotoxicity of DTX-ss-VE loaded liposomes on PC3 (IC50 = 27.5 nM) and A549 cells (IC50 = 63.4 nM) was comparable with the cytotoxicity of DTX-s-VE loaded liposomes (IC50 = 99.2 and 159.5 nM, respectively). The pharmacokinetic studies demonstrated that DTX-ss-VE and DTX-s-VE loaded liposomes exhibited an extended DTX half-life (3.6 +/- 1.2 and 10.0 +/- 3.0 h, respectively) as compared to DTX solutions (2.1 +/- 1.5 h) and an increased AUC (30487.3 +/- 3791.6 and 20922.1 +/- 5633.3 ng/L x h, respectively) compared with DTX solutions (1779.3 +/- 226.6 ng/L x h). Finally, the in vivo anti-tumor studies showed that DTX-ss-VE loaded liposomes possessed similar antitumor activity compared with DTX solutions. Unexpectedly, not any tumor inhibition effect was observed in DTX-s-VE loaded liposomes group. In a conclusion, our studies suggested that simplex favorable properties of the anticancer prodrug can not ensure available good therapeutic index and the rational design of prodrug needs a comprehensive understanding of the in vitro and in vivo behavior of the prodrug. (C) 2016 Elsevier B.V. All rights reserved.
机译：为了获得多西他赛的最佳治疗指数，我们通过酯键与二硫键或硫醚键作为间隔基，使多西他赛（DTX）与维生素E（VE）结合，以生产DTX-ss-VE或DTX-s-VE。将这两种前药成功地装入脂质体中。研究了载有前药的脂质体的理化特性和体外释放曲线。 MIT分析表明，DTX-ss-VE脂质体对PC3（IC50 = 27.5 nM）和A549细胞（IC50 = 63.4 nM）的细胞毒性与DTX-s-VE脂质体的细胞毒性（IC50 = 99.2和159.5）相当分别为nM）。药代动力学研究表明，与DTX溶液相比，DTX-ss-VE和DTX-s-VE脂质体具有更长的DTX半衰期（分别为3.6 +/- 1.2和10.0 +/- 3.0 h）（2.1 + /与DTX溶液（1779.3 +/- 226.6 ng / L xh）相比-1.5小时）和增加的AUC（分别为30487.3 +/- 3791.6和20922.1 +/- 5633.3 ng / L xh）。最后，体内抗肿瘤研究表明，与DTX溶液相比，负载DTX-ss-VE的脂质体具有相似的抗肿瘤活性。出乎意料的是，在载有DTX-s-VE的脂质体组中未观察到任何肿瘤抑制作用。总而言之，我们的研究表明抗癌前药的单方面有利特性不能确保可获得的良好治疗指数，并且前药的合理设计需要对前药的体外和体内行为有全面的了解。 （C）2016 Elsevier B.V.保留所有权利。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号