Biological fate of highly-succinylated N-succinyl-chitosan and antitumor characteristics of its water-soluble conjugate with mitomycin C at i.v. and i.p. administration into tumor-bearing mice

Y. Kato, H. Onishi, Y. Machida

Research output: Contribution to journalArticlepeer-review

Abstract

Highly-succinylated N-succinyl-chitosan (Suc) was fluorescein-labeled, and the labeled product (Suc-FTC) was examined for biodisposition in Sarcoma 180-bearing mice after i.v. and i.p. administration. Suc-FTC injected intravenously was sustained at a high level in the blood circulation and showed little distribution to tissues other than tumor. On the other hand, it took a few hours for Suc-FTC to be transferred to the blood circulation after i.p. administration. There were no marked differences in the distribution of Suc-FTC between i.v. and i.p. administration routes except in the early stage. The urinary excretion of Suc-FTC following both i.v. and i.p. administration was small, but the excretion tended to be suppressed after i.p. administration. Water-soluble Sucmitomycin C conjugate (Suc-MMC) prepared using water-soluble carbodiimide exhibited marked effect at a high dose and suppressed the acute toxic side effect of MMC. Suc-MMC tended to be more toxic at i.p. administration than at i.v. administration. The difference in biodisposition between the two administrations was thought to affect the toxic side effect. The plasma levels of conjugated and free MMCs at 8 h after i.v. administration were higher than those at 8 h after i.p. administration. These suggested more localization of the conjugate in peripheral tissues and less excretion at i.p. administration, which might result in greater toxicity.

Original languageEnglish (US)
Pages (from-to)1497-1503
Number of pages7
JournalBiological and Pharmaceutical Bulletin
Volume23
Issue number12
StatePublished - 2000
Externally publishedYes

Keywords

  • Antitumor characteristics
  • Biodisposition
  • Highly-succinylated N-succinyl-chitosan (Suc)
  • i.p. administration
  • i.v. administration
  • Water-soluble Suc-mitomycin C conjugate

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

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