Abstract: It is reported that conjugated CDDP to polymer carriers can effectively reduce drug's cytotoxicity. In this paper, α,β-poly[(N-succinyl)-L-aspart amide](PSAA) was successfully synthesized via ring cleavage reaction of L-asprtic acid to polysuccinmide in a homogeneous system at room temperature, with the aid of water/triethylamine as a mixed solvent, and characterized by FTIR and ¹H NMR. The influence of volume ratios of water to triethylamine on the reaction was evaluated. PSAA-CDDP and PAsp-CDDP macromolecular prodrugs were prepared with conjugation of PSAA and α,β-poly(L-aspartic acid)(PAsp) with cis-dichlorodiammine platinum(CDDP), respectively. The results show that the cytotoxicity of PSAA or PAsp was rather low. The drugs could be released from PSAA-CDDP or PAsp-CDDP in a controllable manner. The in vitro cytotoxi-city of PSAA-CDDP or PAsp-CDDP against Bel-7402 cells increased with increasing dosage, but was lower than that of CDDP with the corresponding dosage. The cytotoxicity was ranked as PAsp-CDDP<PSAA-CDDP<CDDP.

Key words: α,β-Poly(L-aspartic acid), α,β-Poly[(N-succinyl)-L-aspartamide], cis-Dichlorodiammine platinum(Ⅱ), Macromolecular prodrug, Cytotoxicity