DESIGN OF MACROMOLECULAR PRODRUG OF 5-FLUOROURACIL USING N-ACETYLPOLYGALACTOSAMINE AS A TARGETING CARRIER TO HEPATOMA

Citation
T. Ouchi et al., DESIGN OF MACROMOLECULAR PRODRUG OF 5-FLUOROURACIL USING N-ACETYLPOLYGALACTOSAMINE AS A TARGETING CARRIER TO HEPATOMA, Reactive & functional polymers, 37(1-3), 1998, pp. 235-244
Citations number
17
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Polymer Sciences","Engineering, Chemical","Chemistry Applied
ISSN journal
1381-5148
Volume
37
Issue
1-3
Year of publication
1998
Pages
235 - 244
Database
ISI
SICI code
1381-5148(1998)37:1-3<235:DOMPO5>2.0.ZU;2-Q
Abstract
alpha-1,4-Polygalactosamine (PGA) purified from the culture fluid of P aecilomyces sp. I-1 strain and N-acetylated alpha-1,4-polygalactosamin e (NAPGA) are chitosan- and chitin-like biodegradable, compatible alph a-1,,4-linked polysaccharides, respectively. Partially N-acetylated PG A was found to show the stronger binding activity onto MH134Y hepatoma cells than three kinds of normal lymphocytes, bone marrow, T and B ce lls from the results of binding assay of C-14-50% N-acetylated PGA in vitro. Since PGA and NAPGA have the unreducing end groups of galactosa mine and N-acetyl galactosamine, respectively, they were suggested to exhibit the receptor-mediated affinities to hepatoma cells. In order t o provide the lysosomotropic macromolecular prodrug of fluorouracil (5 FU) having a targeting ability to hepatoma, we synthesized water-solub le 6-O-carboxymethyl-NAPGA-immobilized 5FUs through Gly-Phe-Leu-Gly, m onomethylene spacer groups. The obtained conjugate showed the cathepsi n-B-susceptible release behavior of 5FU and then exhibited the stronge r cytotoxic activity than free 5FU against HLE hepatoma cells in vitro . (C) 1998 Elsevier Science B.V. All rights reserved.