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Synthesis of antitumor‐active conjugates of adriamycin or daunomycin with the copolymer of divinyl ether and maleic anhydride

 

作者: Takashi Hirano,   Shinichi Ohashi,   Satoshi Morimoto,   Keishiro Tsuda,   Tomowo Kobayashi,   Shigeru Tsukagoshi,  

 

期刊: Die Makromolekulare Chemie  (WILEY Available online 1986)
卷期: Volume 187, issue 12  

页码: 2815-2824

 

ISSN:0025-116X

 

年代: 1986

 

DOI:10.1002/macp.1986.021871208

 

出版商: Hüthig&Wepf Verlag

 

数据来源: WILEY

 

摘要:

AbstractPolymeric conjugates of adriamycin (ADR) (2) or daunomycin (DM) (3) were synthesized by reaction of the drugs with the copolymer of divinyl ether and maleic anyhdride (DIVEMA) (1). The content of ADR moieties in the DIVEMA conjugate (4) could be varied depending on the reaction conditions up to 35,8 wt.‐%. Considering the low toxicity and the high possibility of renal excretion, DIVEMA with M̄wof 7000 and M̄w/M̄n= 1,6 was used for the conjugation. The rate of drug release from the conjugate was determined under physiological conditions by reversed phase HPLC. Within 14 days only 15% of the attached ADR was released from conjugate4. The antitumor activity of the conjugates was tested in vitro and in vivo against mouse P388 leukemia. Conjugate4proved to be 28 times less active than ADR in vitro, which could be explained from the slow drug‐release. On the contrary 50% of the leukemic mice treated by4survived more than 60 days, whereas no mice given ADR alone or the admixture of ADR and DIVEMA survived 30 days. An antitumor activity of the polymeric conjugate better than that of the free drug was also observed in vivo with DM. Such a polymeric effect can be attributed either to the change in body distribution, the difference in pharmacokinetics, or the slow drugr

 

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