| Project/Area Number |
02650672
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
高分子合成
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| Research Institution | Kansai University |
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Principal Investigator |
OUCHI Tatsuro Kansai University, Faculty of Engineering Professor, 工学部, 教授 (60067650)
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| Co-Investigator(Kenkyū-buntansha) |
OHYA Yuichi Kansai University, Faculty of Engineering Instructor, 工学部, 助手 (10213886)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1990: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Macromolecular Prodrug / Poly (Malic Acid) / Chitosan / Polygalactosamine / 5-Fluorouracil / Saccharide / Release Rate / Antitumor Activity / キチン / 生体内分解性高分子 / PEG |
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| Research Abstract |
5-Fluorouracil (5FU) has a remarkable antitumor activity, which is accompanied, however, by undesirable side-effects. Poly (malic acid), chitosan and polygalactosamine are of interest for application as low or non-toxic, compatible and biodegradable carriers of macromolecular prodrug. In order to provide a macromolecular prodrug of 5FU reducing the side-effects, having affinity for tumor cells and exhibiting strong antitumor activity, the covalent attachment of 5FUs to poly (malic acid) /sa. ccharide, chitosamino-oligosaccharide and polygalactosam ine through hydrophobic methylene spacer groups via urea or ester bonds was carried out.
The obtained conjugates were found to be hydrolyzed to release free 5FU itself at 37ﾟC in vitro. These biodegradable polymer/5FU conjugates exhibited strong survival effects against p388 lymphocytic leukemia in mice by intraperitoneal (ip) transiplantation / ip injection in vivo. Moreover, these conjugates did not display any acute toxicity even in the high dose ranges. Poly (malic acid) /5FU /galactosamine and polygalactosamine /5FU exhibited high growth-inhibitory effects against hepatoma cells in vitro th an the other conjugates obtained. Such an appearance of high growth-inhibitory for the conjugate of 5FU/polymer having galactosamine residues against hepatoma cells can be explained by galactose receptor-mediated selective uptake into the hepatoma cells.
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