Binding of anthracycline derivatives to human serum lipoproteins.

The binding of eight anthracycline analogues (including mitoxantone) to isolated serum lipoproteins (high, low and very low density lipoproteins) was studied in order to elucidate some determinants of their interaction with lipidic structures. Serum lipoproteins were isolated by ultracentrifugation. Drug binding experiments were run by ultrafiltration at 37 o C and pH 7.4. Anthracycline concentrations (total and free) were determined by HPLC with fluorometric detection. All the ligands were significantly bound to the three lipoprotein classes, and for each ligand the binding increased as the lipidic fraction of lipoprotein increased. From doxorubicin; to iododoxorubicin, there was a tenfold increase in lipoprotein binding (doxorubicinepirubicin<daunorubicin<pirarubicin<aclarubicin<zorubicinlipoprotein binding appears to be related to chemical determinants of lipophilicity