1994 Fiscal Year Final Research Report Summary
Development on Selective Delivery System of Antitumor Agents by Utilizing Cell-Recognition Ability of Saccharides
| Project/Area Number |
05680767
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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 |
Biomedical engineering/Biological material science
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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, Assistant, 工学部, 助手 (10213886)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Saccharide / Cell-Recognition Ability / Macromolecular Prodrug / Carrier / Biodegradable-Absorbable Polymer / Antitumor Agent / Peptide Spacer / Lysosomal Enzyme |
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| Research Abstract |
Poly (alpha-malic acid) is of interest as a biodegradable and bioadsorbable poly (lactide) type drug carrier, which is able to covalently attach both drug and targeting moiety. The macromolecular prodrug of antitumor drug will reduce the side-effects, have the ability to target tumor cells and exhibit high antitumor activity. The design of poly (alpha-malic acid) /5-fluorouracil (5FU) /saccharide and poly (alpha-malic acid) /adriamycin (ADR) /saccharide conjugates were investigated. Monosaccharides such as galactosamine, glucosamine and mannosamine were used as targeting moieties. Growth inhibition against various tumor cells in vitro and the survival effect against mice bearing tumor cells in vivo were tested. Poly (alpha-malic acid) /5FU/galactosamine and poly (alpha-malic acid) /ADR/galactosamine conjugates showed stronger growth-inhibitory effects than poly (alpha-malic acid) /5FU and poly (alpha-malic acid) /ADR conjugates against human hepatoma cells in vitro. These results could be explained by galactose receptor-mediated specific uptake into hepatocyte cells. Moreover, the conjugates of poly (alpha-malic acid) with 5FU exhibited significant survival effects against p388 lymphocytic leukemia in mice by intraperitoneal (ip) transplantation/ip injection. The obtained conjugates did not display an acute toxicity in the high dose ranges.
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