Cytotoxic effect of a lipophilic alkylating agent after incorporation into low density lipoprotein or emulsions: studies in human leukemic cells.
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.
Masquelier
Michèle
M
Department of Medicine, Division of Clinical Pharmacology, Karolinska Institute/Karolinska University Hospital, S-171 76 Stockholm, Sweden. michele.masquelier@medks.ki.se
Lundberg
Bo
B
Peterson
Curt
C
Vitols
Sigurd
S
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
D018906:Antineoplastic Agents, Alkylating; D004337:Drug Carriers; D004655:Emulsions; D008077:Lipoproteins, LDL; D009588:Nitrogen Mustard Compounds; D019301:Oleic Acid; C066486:WB 4291; D008558:Melphalan