Role of formulation composition in folate receptor-targeted liposomal doxorubicin delivery to acute myelogenous leukemia cells
Role of formulation composition in folate receptor-targeted liposomal doxorubicin delivery to acute myelogenous leukemia cells
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DOI：
10.1021/mp070058l
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发表时间：
2007-09-01
影响因子：
4.9
通讯作者：
Lee, Robert J.
中科院分区：
文献类型：
--
作者：
Lu, Yanhui;Wu, Jun;Lee, Robert J.
靶向药物递送具有提高治疗剂的功效同时减少其副作用的潜力。叶酸受体β型（FR-β）是一种细胞表面标志物，在约70%的急性髓性白血病（AML）患者的白血病细胞中选择性表达。全反式维甲酸（ATRA）处理也可以选择性地诱导AML细胞中FR-β的上调。在该研究中，研究了制剂组合物在向AML细胞递送FIR靶向脂质体多柔比星（DOX）中的作用。合成了具有可变百分比的叶酸-聚乙二醇二硬脂酰磷脂酰乙醇胺（f-PEG-DSPE）的脂质体制剂，并在体外评价了在MV 4 -11 AML细胞中FR-β靶向DOX递送及其体内药代动力学性质。含有0.5 mol % f-PEG-DSPE的制剂表现出最高的细胞摄取效率和体外细胞毒性，以及在小鼠中的较长的体循环时间。在MV 4 -11细胞中，基于该制剂的FR靶向脂质体DOX的结合和细胞毒性也通过ATRA诱导的FR-β上调而增强。
Targeted drug delivery has the potential to improve the efficacy of a therapeutic agent while reducing its side effects. The folate receptor type beta (FR-beta) is a cell surface marker selectively expressed in the leukemic cells of approximately 70% of acute myeloid leukemia (AML) patients. Upregulation of FR-beta may also be selectively induced in AML cells by treatment with all-trans-retinoic acid (ATRA). In this study, the role of formulation composition in FIR-targeted liposomal doxorubicin (DOX) delivery to AML cells was investigated. Liposomal formulations with a variable percentage of folate-polyethylene glycol distearoyl phosphatidylethanolamine (f-PEG-DSPE) were synthesized and evaluated for FR-beta-targeted DOX delivery in MV4-11 AML cells in vitro and for their pharmacokinetic properties in vivo. The formulation containing 0.5 mol % f-PEG-DSPE exhibited the highest efficiency of cellular uptake and in vitro cytotoxicity, as well as a long systemic circulation time in mice. In MV4-11 cells, the binding and cytotoxicity of FR-targeted liposomal DOX based on this formulation was also enhanced by ATRA-induced FR-beta upregulation.