...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biomedicine & pharmacotherapy =: Biomedecine & pharmacotherapie >Investigation of the antitumor activity and toxicity of long-circulating and fusogenic liposomes co-encapsulating paclitaxel and doxorubicin in a murine breast cancer animal model
【24h】

Investigation of the antitumor activity and toxicity of long-circulating and fusogenic liposomes co-encapsulating paclitaxel and doxorubicin in a murine breast cancer animal model

机译：在鼠乳腺癌动物模型中共用紫杉醇和多柔比蛋白的长循环和致致沉膜脂质体的抗肿瘤活性和毒性研究

获取原文
获取原文并翻译 | 示例
   

获取外文期刊封面封底 >>

       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

To associate paclitaxel (PTX) with doxorubicin (DXR) is one of the main chemotherapy strategies for breast cancer (BC) management. Despite the high response rates for this combination, it presents a cardiotoxic synergism, attributed to pharmacokinetic interactions between PTX and both DXR and its metabolite, doxorubicinol. One of the main strategies to minimize the cardiotoxicity of the combination is to extend the interval of time between DXR and PTX administration. However, it has been previously suggested that their co-administration leads to better efficacy compared to their sequential administration. In the present study, we investigated different molar ratio combinations of PTX:DXR (10:1; 1:1, and 1:10) against the 4T1 murine breast cancer cell line and concluded that there is no benefit of enhancing PTX concentration above that of DXR on the combination. Therefore, we obtained a long-circulating and fusogenic liposomal formulation co-encapsulating PTX and DXR (LCFL-PTX/DXR) at a molar ratio of 1:10, respectively, which maintained the in vitro biological activity of the combination. This formulation was investigated for its antitumor activity and toxicity in Balb/c mice bearing 4T1 breast tumor, and compared to treatments with free PTX, free DXR, and the mixture of free PTX:DXR at 1:10 molar ratio. The higher tumor inhibition ratios were observed for the treatments with free and co-encapsulated PTX:DXR in liposomes (66.87 and 66.52%, respectively, P 0.05) as compared to the control. The great advantage of the treatment with LCFL-PTX/DXR was its improved cardiac toxicity profile. While degeneration was observed in the hearts of all animals treated with the free PTX:DXR combination, no signs of cardiac toxicity were observed for animals treated with the LCFL-PTX/DXR. Thus, LCFL-PTX/DXR enables the co-administration of PTX and DXR, and might be considered valuable for breast cancer management.
机译：将Paclitaxel（PTX）与多柔比星（DXR）相关联（DXR）是乳腺癌（BC）管理的主要化疗策略之一。尽管对这种组合的响应率高，但它呈现出心脏毒性的协同作用，其归因于PTX和DXR和其代谢物之间的药代动力学相互作用，并且其代谢物，多柔霉素。最小化组合的心脏毒性的主要策略之一是延长DXR和PTX管理之间的时间间隔。然而，先前已经表明他们的共同施用与顺序给药相比导致更好的疗效。在本研究中，我们研究了PTX：DXR（10：1; 1：1和1:10）的不同摩尔比和1:10，并得出结论，没有益处提高PTX浓度以上DXR在组合上。因此，我们将长循环和致密性脂质体配方共同包封PTX和DXR（LCFL-PTX / DXR）以分别为1:10的摩尔比，其保持了组合的体外生物活性。研究了这种制剂，用于携带4T1乳腺肿瘤的BALB / C小鼠中的抗肿瘤活性和毒性，并与1:10摩尔比的游离PTX，游离DXR和游离PTX：DXR的混合物进行比较。与对照相比，在脂质体中具有自由和共涂化的PTX的处理（分别为66.87和66.52％，P＆GT; 0.05），观察到较高的肿瘤抑制比。用LCFL-PTX / DXR处理的巨大优点是其改善的心脏毒性曲线。虽然在用自由PTX治疗的所有动物的心脏中观察到退化：DXR组合，但对于用LCFL-PTX / DXR处理的动物没有观察到心脏毒性的迹象。因此，LCFL-PTX / DXR能够共同施用PTX和DXR，并且可能被认为对乳腺癌管理有价值。

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