title: Cytotoxic effect of a lipophilic alkylating agent after incorporation into low density lipoprotein or emulsions: studies in human leukemic cells.
abstract: The use of low density lipoprotein (LDL) as drug carrier in acute myeloblastic leukemia chemotherapy is attractive due to high LDL uptake by leukemic cells. Lipid-based formulations, such as liposomes or microemulsions are promising alternatives. In the current study, we incorporated N-trifluoroacetyl-adriamycin-14-valerate (AD32), a lipophilic derivative of daunorubicin (DNR), and WB4291, a lipophilic alkylating agent, into LDL or lipid microemulsions and evaluated their cytotoxic activities towards leukemic cell lines using as references DNR and melphalan. The incorporation of AD32 into LDL or emulsion resulted in complexes with poor cytotoxicity. WB4291-LDL and WB4291-emulsion exerted, on the other hand, promising cytotoxic effects towards parental and resistant K562 and HL60 cell lines.
authors.affiliation: Department of Medicine, Division of Clinical Pharmacology, Karolinska Institute/Karolinska University Hospital, S-171 76 Stockholm, Sweden. michele.masquelier@medks.ki.se
authors.forename: Michèle
authors.initials: M
authors.lastname: Masquelier
authors.forename: Bo
authors.initials: B
authors.lastname: Lundberg
authors.forename: Curt
authors.initials: C
authors.lastname: Peterson
authors.forename: Sigurd
authors.initials: S
authors.lastname: Vitols
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D004337:Drug Carriers; D004355:Drug Stability; D004655:Emulsions; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D008077:Lipoproteins, LDL / Q000008:administration & dosage*; D008558:Melphalan / Q000008:administration & dosage; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage; D019301:Oleic Acid / Q000008:administration & dosage
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004337:Drug Carriers; D004655:Emulsions; D008077:Lipoproteins, LDL; D009588:Nitrogen Mustard Compounds; D019301:Oleic Acid; C066486:WB 4291; D008558:Melphalan