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Masquelier, M. et al.

Masquelier, Tirzitis, Peterson, Pålsson, Amolins, Plotniece, Plotniece, Makarova, Vitols,

Plasma stability and cytotoxicity of lipophilic daunorubicin derivatives incorporated into low density lipoproteins.

The selective targeting of antineoplastic drugs to tumours by incorporation in low density lipoproteins (LDL) is an attractive possibility if the drug-LDL complex remains stable in the circulation and is taken up by the tumour. In previous studies we have shown that vincristine- and N-trifluoroacetyladriamycin-14-valerate-LDL complexes were unstable in vivo. We synthesized five N-substituted lipophilic derivatives of daunorubicin and studied their incorporation into LDL. Three out of five daunorubicin derivatives incorporated successfully into LDL. In vitro these complexes were more cytotoxic towards LDL receptor positive Chinese hamster ovary cells than LDL receptor negative cells. Non-specific cytotoxicity was explained by slow dissociation of the drug-LDL complex in plasma. Our results underline the importance of careful studies of plasma stability when investigating lipoproteins and other carriers in drug targeting.[1]

References

Plasma stability and cytotoxicity of lipophilic daunorubicin derivatives incorporated into low density lipoproteins. Masquelier, M., Tirzitis, G., Peterson, C.O., Pålsson, M., Amolins, A., Plotniece, M., Plotniece, A., Makarova, N., Vitols, S.G. European journal of medicinal chemistry. (2000) [Pubmed]

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