Role of Formulation Composition in Folate Receptor-Targeted Liposomal Doxorubicin Delivery to Acute Myelogenous Leukemia Cells

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• 作者：Yanhui Lu ; Jun Wu ; Jianmei Wu ; Mefsin Gonit ; Xiaojuan Yang ; Alice Lee ; Guangya Xiang ; Hong Li ; Shujun Liu ; Guido Marcucci ; Manohar Ratnam ; Robert J. Lee
• 刊名：Molecular Pharmaceutics
• 出版年：2007
• 出版时间：October 2007
• 年：2007
• 卷：4
• 期：5
• 页码：707 - 712
• 全文大小：234K
• 年卷期：v.4,no.5(October 2007)
• ISSN：1543-8392

文摘

Targeted drug delivery has the potential to improve the efficacy of a therapeutic agent while reducing its side effects. The folate receptor type β (FR-β) is a cell surface marker selectively expressed in the leukemic cells of approximately 70% of acute myeloid leukemia (AML) patients. Upregulation of FR-β 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 FR-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-β-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-β upregulation.