...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of drug targeting >Coencapsulation of alendronate and doxorubicin in pegylated liposomes: a novel formulation for chemoimmunotherapy of cancer
【24h】

Coencapsulation of alendronate and doxorubicin in pegylated liposomes: a novel formulation for chemoimmunotherapy of cancer

机译：聚乙二醇化脂质体中的Alendronate和多柔比星的Coorcapucation：一种新型癌症化疗疗法的制剂

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

We developed a pegylated liposome formulation of a dissociable salt of a nitrogen-containing bisphosphonate, alendronate (Ald), coencapsulated with the anthracycline, doxorubicin (Dox), a commonly used chemotherapeutic agent. Liposome-encapsulated ammonium Ald generates a gradient driving Dox into liposomes, forming a salt that holds both drugs in the liposome water phase. The resulting formulation (PLAD) allows for a high-loading efficiency of Dox, comparable to that of clinically approved pegylated liposomal doxorubicin sulfate (PLD) and is very stable in plasma stability assays. Cytotoxicity tests indicate greater potency for PLAD compared to PLD. This appears to be related to a synergistic effect of the coencapsulated Ald and Dox. PLAD and PLD differed in in vitro monocyte-induced IL-1 release (greater for PLAD) and complement activation (greater for PLD). A molar ratio Ald/Dox of approximate to 1:1 seems to provide an optimal compromise between loading efficiency of Dox, circulation time and in vivo toxicity of PLAD. In mice, the circulation half-life and tumor uptake of PLAD were comparable to PLD. In the M109R and 4T1 tumor models in immunocompetent mice, PLAD was superior to PLD in the growth inhibition of subcutaneous tumor implants. This new formulation appears to be a promising tool to exploit the antitumor effects of aminobisphosphonates in synergy with chemotherapy.
机译：我们开发了一种聚吡酰胺化脂质体制型含氮的双膦酸盐，醛膦酸盐（ALD），与蒽环类，多柔枯蛋白（DOX），常用的化学治疗剂的常用盐。脂质体包封的铵ALD产生梯度驱动DOX进入脂质体，形成含有脂质体水相中的两种药物的盐。所得制剂（PLAD）允许DOX的高负荷效率，与临床批准的聚乙二醇化脂质体DOXORUBICIN硫酸盐（PLD）的高负载效率相当，并且在等离子体稳定性测定中非常稳定。与PLD相比，细胞毒性试验表明Plad的更大效力。这似乎与Coencapsulated ALD和DOX的协同效果有关。 Plad和PLD在体外单核细胞诱导的IL-1释放（较大的PLAD）和补体激活（PLD更大）。摩尔比Ald / dox近似为1：1似乎在Dox，循环时间和副毒性的体内毒性之间提供了最佳的折衷。在小鼠中，循环半衰期和肿瘤的血栓摄取与PLD相当。在免疫活性小鼠的M109R和4T1肿瘤模型中，Plad优于皮下肿瘤植入物的生长抑制。这种新的配方似乎是一个有希望的工具，用于利用氨基双膦酸酯在化疗中的协同作用中的抗肿瘤作用。

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