Cytotoxic activity of a new lipid formulation of doxorubicin in cell lines and primary tumor cells.
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.
Gullbo
Joachim
J
Division of Clinical Pharmacology, Akademiska Hospital, Uppsala University, SE-751 85 Uppsala. Sweden.
Arsenau
Dzimitry
D
Grundmark
Birgitta
B
Alvfors
Carina
C
Larsson
Rolf
R
Lindhagen
Elin
E
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
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