title: Cytotoxic activity of a new lipid formulation of doxorubicin in cell lines and primary tumor cells.
abstract: BACKGROUND
  Liposomal formulations of the anthracyclines are being developed to circumvent toxicity and prolong effect. The current study investigates the in vitro activity of a novel doxorubicin micelle formulation, containing a vehicle designed to release pharmacologically active subcomponents.
  
  
  METHODS
  The cytotoxicity of doxorubicin formulated in a vehicle containing C4 (N-docosahexaenoyl-O-phospho-2-aminoethanol) and C11 (N-all trans-retinoyl-O-phospho-L-tyrosine) was measured in a panel of human tumor cell lines, 19 primary cultures of human tumor cells and 5 lymphocyte preparations.
  
  
  CONCLUSIONS
  At the tested ratio between doxorubicin and C4/C11 (1:50), C4/C11 contributed significantly to the in vitro toxicity. However, the molar EC50-values were lower for doxorubicin than for C4/C11. Synergistic interactions between doxorubicin and C4/C11 were evident in a majority of the cell types studied. C4/C11 increased the cellular load of the fluorescent Pgp substrate calcein. To further investigate the possible benefits of the new formulation, in vivo studies are ongoing.
authors.affiliation: Division of Clinical Pharmacology, Akademiska Hospital, Uppsala University, SE-751 85 Uppsala. Sweden.
authors.forename: Joachim
authors.initials: J
authors.lastname: Gullbo
authors.forename: Dzimitry
authors.initials: D
authors.lastname: Arsenau
authors.forename: Birgitta
authors.initials: B
authors.lastname: Grundmark
authors.forename: Carina
authors.initials: C
authors.lastname: Alvfors
authors.forename: Rolf
authors.initials: R
authors.lastname: Larsson
authors.forename: Elin
authors.initials: E
authors.lastname: Lindhagen
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D004983:Ethanolamines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008823:Micelles; D019000:Phosphotyrosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004983:Ethanolamines; D008823:Micelles; C471709:N-docosahexaenoyl-O-phospho-2-aminoethanol; C471710:N-retinoyl-O-phosphotyrosine; D019000:Phosphotyrosine; D014443:Tyrosine; D004317:Doxorubicin