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 journalArticlepeer-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 languageEnglish (US)
Pages (from-to)707-712
Number of pages6
JournalMolecular pharmaceutics
Volume4
Issue number5
DOIs
StatePublished - Sep 2007
Externally publishedYes

Keywords

  • All-trans-retinoic acid
  • Doxorubicin
  • Folate receptor
  • Liposomes

Fingerprint

Dive into the research topics of 'Role of formulation composition in folate receptor-targeted liposomal doxorubicin delivery to acute myelogenous leukemia cells'. Together they form a unique fingerprint.

Cite this