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 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 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-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.
authors: Division of Pharmaceutics, College of Pharmacy, Department of Internal Medicine, The Ohio State University, 500 W. 12th Avenue, Columbus, OH 43210, USA.
authors: Yanhui
authors: Y
authors: Lu
authors: Jun
authors: J
authors: Wu
authors: Jianmei
authors: J
authors: Wu
authors: Mefsin
authors: M
authors: Gonit
authors: Xiaojuan
authors: X
authors: Yang
authors: Alice
authors: A
authors: Lee
authors: Guangya
authors: G
authors: Xiang
authors: Hong
authors: H
authors: Li
authors: Shujun
authors: S
authors: Liu
authors: Guido
authors: G
authors: Marcucci
authors: Manohar
authors: M
authors: Ratnam
authors: Robert J
authors: RJ
authors: Lee
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D008081:Liposomes; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D014212:Tretinoin; D004317:Doxorubicin