Synthesis and cytotoxic activity of doxorubicin bound to poly(α‐malic acid) via ester or amide bonds

Poly(α‐malic acid) is of interest for the application as a biodegradable and bioadsorbable drug carrier, which has pendent reactive carboxylic acid groups. In order to provide a biodegradable macromolecular prodrug of doxorubicin (adriamycin, ADR), reducing the side‐effects of ADR and exhibiting effective antitumor activity, ADR residues were covalently attched to poly(α‐malic acid) via ester or amide bonds to give poly(α‐malic acid)/ester/ADR conjugate 1 or poly(α‐malic acid)/amide/ADR conjugate 2 , respectively. The release rate of ADR from the poly(α‐malic acid)/ester/ADR conjugate 1 was faster than that from the poly(α‐malic acid)/amide/ADR conjugate 2 in buffer solution (pH 7,4) at 37°C. While the cytotoxic activity of poly(α‐malic acid)/ester/ADR conjugate 1 is as strong as that of free ADR against p388D 1 lymphocytic leukemia cells in vitro, the cytotoxic activity of poly(α‐malic acid)/amide/ADR conjugate 2 is much lower.