Leukemia Research
Volume 30, Issue 2 , Pages 136-144, February 2006

Cytotoxic effect of a lipophilic alkylating agent after incorporation into low density lipoprotein or emulsions: Studies in human leukemic cells

  • Michèle Masquelier

      Affiliations

    • Department of Medicine, Division of Clinical Pharmacology, Karolinska Institute/Karolinska University Hospital, S-171 76 Stockholm, Sweden
    • Corresponding Author InformationCorresponding author. Tel.: +46 851774461; fax: +46 8331343.
  • ,
  • Bo Lundberg

      Affiliations

    • Department of Biochemistry and Pharmacy, Åbo Akademi University, BioCity, P.O. Box 66, 20520 Åbo, Finland
  • ,
  • Curt Peterson

      Affiliations

    • Division of Clinical Pharmacology, Department of Medicine and Care, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden
  • ,
  • Sigurd Vitols

      Affiliations

    • Department of Medicine, Division of Clinical Pharmacology, Karolinska Institute/Karolinska University Hospital, S-171 76 Stockholm, Sweden

Received 11 April 2005; received in revised form 17 June 2005; accepted 18 June 2005. published online 07 March 2011.

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.

Keywords: LDL, Lipid emulsion, Acute myeloid leukemia, DNR, Melphalan

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PII: S0145-2126(05)00228-6

doi:10.1016/j.leukres.2005.06.012

Leukemia Research
Volume 30, Issue 2 , Pages 136-144, February 2006