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1994 Fiscal Year Final Research Report Summary

Development on Selective Delivery System of Antitumor Agents by Utilizing Cell-Recognition Ability of Saccharides

Research Project

Project/Area Number 05680767
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Biomedical engineering/Biological material science
Research InstitutionKANSAI UNIVERSITY

Principal Investigator

OUCHI Tatsuro  Kansai University, Faculty of Engineering, Professor, 工学部, 教授 (60067650)

Co-Investigator(Kenkyū-buntansha) OHYA Yuichi  Kansai University, Faculty of Engineering, Assistant, 工学部, 助手 (10213886)
Project Period (FY) 1993 – 1994
KeywordsSaccharide / Cell-Recognition Ability / Macromolecular Prodrug / Carrier / Biodegradable-Absorbable Polymer / Antitumor Agent / Peptide Spacer / Lysosomal Enzyme
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.

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] 大矢裕一: "Synthesis of a MDP Analogue/Chitin Conjugate That Stimulates Cultured Macrophages" J.Bioact.Compat.Polym.8. 351-364 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 大矢裕一: "Immunological Enhancement Activity of Muramyl Dipeptide Analogue/CM-Curdlan Conjugate" Carbohydr.Polym.23. 47-54 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 大矢裕一: "Release Behavior of 5-Fluorouracil from Chitosan-Gel Microspheres Immobilizing 5-Fluorouracil Coated with Polysaccharides and Their Cell Specific Cytotoxicity" J.Macromol.Sci.-Pure Appl.Chem.A31. 629-642 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 大矢裕一: "Synthesis of CM-Chitin Immobilizing Doxorubicins through Tetrapeptide Spacer Groups and Its Enzymatic Release Behavior of Doxorubicin in Vitro" Macromol.Chem.Phys.195. 2839-2853 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 大内辰郎(分筆): "Am.Chem.Soc." ACS Symposium Series 520. 411 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 大内辰郎(分筆): "Am.Chem.Soc." ACS Symposium Series 545. 246 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 大内辰郎(分筆): "Biotechnology and Bioactive polymers" Plenum Press, 342 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 大内辰郎(分筆): "Neoglycoconjugates:Preparation and Application" Academic Press, 549 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yuichi Ohya: "Synthesis of a MDP Analogue/Chitin Conjugate That Stimulates Cultured Macrophages" J.Bioact. Compat. polym.8. 351-364 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yuichi Ohya: "Immunological Enhancement Activity of Muramyl Dipeptide Analogue/CM-Curdlan Conjugate" Carbohydr. Polym.23. 47-54 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yuichi Ohya: "Release Behavior of 5-Fluorouracil from Chitosan-Gel Microspheres Immobilizing 5-Fluorouracil Coated with Polysaccharides and Their Cell Specific Cytotoxicity" J.Macromol. Sci. -Pure Appl. Chem.A31. 629-642 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yuichi Ohya: "Synthesis of CM-Chitin Immobilizing Doxorubicins through Tetrapeptide Spacer Groups and Its Enzymatic Release Behavior of Doxorubicin in Vitro" Macromol. Chem. Phys.195. 2839-2853 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tatsuro Ouchi: ACS Symposium Series 520. Am. Chem. Soc., 411 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tatsuro Ouchi: ACS Symposium Series 545. Am. Chem. Soc., 246

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tatsuro Ouchi: Biotechnology and Bioactive Polymers. Plenum Press, 342 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tatsuro Ouchi: Neoglycoconjugates : Preparation and Application. Academic Press, 549 (1994)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1996-04-15  

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