Journal
BIOMATERIALS
Volume 21, Issue 15, Pages 1579-1585Publisher
ELSEVIER SCI LTD
DOI: 10.1016/S0142-9612(00)00044-2
Keywords
N-succinyl-chitosan; systemic retention; body distribution; urinary excretion; tumor accumulation
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The water-soluble, low toxic and less biodegradable chitosan derivative N-succinyl-chitosan (Suc-chitosan) was investigated for body distribution and urinary excretion on a long-time scale (24-72 h after i.v. injection) using a fluorescein-labeling technique. Fluorescein isothiocyanate (FITC)-labeled Suc-chitosan (Suc-chitosan-FTC) was characterized for molecular weight, succinylation degree and FTC content. Systemic retention and tissue distribution of Suc-chitosan-FTC were examined after i.v. administration to normal and Sarcoma 180 tumor-bearing mice. Suc-chitosan-FTC was sustained at a high level in the circulation over 72 h; that is, the plasma half-life in normal mice was 100.3 h and that in tumor-bearing mice was 43.0 h, which was longer than those of other long-circulating macromolecules reported to date. As to the tissues except blood circulation, Suc-chitosan-FTC was distributed very little in tissues other than the turner. Although the total amount of Suc-chitosan-FTC residing in tested tissues decreased gradually, urinary excretion did not increase from 24 h after injection. These observations suggested that Suc-chitosan-FTC may be eliminated by mechanisms other than in the urine or moved to tissues other than those tested. The ratio of tumor accumulation reached a plateau at 48 h after injection, and the accumulation level, approximately 10%, was similar to those observed for other reported long-circulating macromolecules. (C) 2000 Elsevier Science Ltd. All rights reserved.
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