Role of formulation composition in folate receptor-targeted liposomal doxorubicin delivery to acute myelogenous leukemia cells

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

doi:10.1021/mp070058l

Role of formulation composition in folate receptor-targeted liposomal doxorubicin delivery to acute myelogenous leukemia cells

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

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	707-712
Number of pages	6
Journal	Molecular pharmaceutics
Volume	4
Issue number	5
DOIs	https://doi.org/10.1021/mp070058l
State	Published - Sep 2007
Externally published	Yes

Keywords

All-trans-retinoic acid
Doxorubicin
Folate receptor
Liposomes

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title = "Role of formulation composition in folate receptor-targeted liposomal doxorubicin delivery to acute myelogenous leukemia cells",

abstract = "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.",

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author = "Yanhui Lu and Jun Wu and Jianmei Wu and Mefsin Gonit and Xiaojuan Yang and Alice Lee and Guangya Xiang and Hong Li and Shujun Liu and Guido Marcucci and Manohar Ratnam and Lee, {Robert J.}",

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AU - Lu, Yanhui

AU - Wu, Jun

AU - Wu, Jianmei

AU - Gonit, Mefsin

AU - Yang, Xiaojuan

AU - Lee, Alice

AU - Xiang, Guangya

AU - Li, Hong

AU - Liu, Shujun

AU - Marcucci, Guido

AU - Ratnam, Manohar

AU - Lee, Robert J.

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N2 - 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.

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Role of formulation composition in folate receptor-targeted liposomal doxorubicin delivery to acute myelogenous leukemia cells

Abstract

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UN SDGs

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