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.

MATERIALS AND 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.

RESULTS AND CONCLUSION:

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: Joachim Gullbo, Dzimitry Arsenau, Birgitta Grundmark, Carina Alvfors, Rolf Larsson, Elin Lindhagen
• Journal: Anticancer research (Anticancer Res) 2002 Nov-Dec Vol. 22 Issue 6C Pg. 4191-8 ISSN: 0250-7005 [Print] Greece
• PMID: 12553055 (Publication Type: Journal Article)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antineoplastic Agents
• Ethanolamines
• Micelles
• N-docosahexaenoyl-O-phospho-2-aminoethanol
• N-retinoyl-O-phosphotyrosine
• Phosphotyrosine
• Tyrosine
• Doxorubicin

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
• Antineoplastic Agents (chemistry, pharmacokinetics, pharmacology)
• Doxorubicin (chemistry, pharmacokinetics, pharmacology)
• Drug Screening Assays, Antitumor
• Drug Synergism
• Ethanolamines (chemistry, pharmacokinetics, pharmacology)
• Humans
• Micelles
• Phosphotyrosine (analogs & derivatives, chemistry, pharmacokinetics, pharmacology)
• Tumor Cells, Cultured (drug effects)
• Tyrosine (analogs & derivatives, pharmacology)