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. 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.[1]References
- Cytotoxic activity of a new lipid formulation of doxorubicin in cell lines and primary tumor cells. Gullbo, J., Arsenau, D., Grundmark, B., Alvfors, C., Larsson, R., Lindhagen, E. Anticancer Res. (2002) [Pubmed]
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