Comparison of antitumor effects of daunorubicin covalently linked to poly-L-amino acid carriers.

Daunorubicin was covalently linked to poly-L-aspartic and poly-L-lysine of different molecular weights via the methylketone side-chain of the drug by the use of a method that employs the 14-bromo derivative of the antibiotic. During reaction ester and C-N linkages were formed with poly-L-aspartic acid and poly-L-lysine respectively. Whereas a reduction of drug toxicity was observed with both types of conjugate, only the linking to the anionic polymer produced an enhancement of drug activity. In contrast, when drug was covalently attached to poly-L-lysine, cytotoxic activity and in vivo potency and efficacy were markedly reduced. The different therapeutic properties of these conjugates can be explained in terms of the different nature and stability of chemical bonds formed between the drug and the amino groups and carboxyl functions of the polyamino acid carrier.