Abstract
Doxorubicin (adriamycin; ADR) which is one of the most clinically used antitumor agent, has undesirable side-effects. To reduce these side-effects, a macromolecular prodrug of ADR exhibiting high antitumor activity, the conjugate of PEG end-capped with ADR was developed. Tb effect intracellular release of ADR from the conjugate, ester, amide and Schiffs base bonds were employed as modes of bonding ADR to PEG. The MeO-PEG/Schiffs base/ADR conjugate readily released ADR under the lysosomal acidic conditions in vitro and very slowly ADR under physiological conditions. Moreover, the MeO-PEG/Schiffs base/ADR conjugate showed strong cytotoxic activity similar to free ADR against p388D1 lymphocytic leukemia cells in vitro. Fluorescence measurements suggest that the conjugate forms self-aggregates in aqueous solution.
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