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Targeting of anticancer drugs and genome medicine by utilizing absorption from the liver surface

Research Project

Project/Area Number 14572033
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Physical pharmacy
Research InstitutionNagasaki University

Principal Investigator

NISHIDA Koyo  Nagasaki University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (20237704)

Co-Investigator(Kenkyū-buntansha) NAKASHIMA Mikiro  Nagasaki University Hospital of Medicine and Dentistry, Department of Hospital Pharmacy, Associate Professor, 医学部・歯学部附属病院, 助教授 (00260737)
KAWAKAMI Shieru  Kyoto University, Graduate School of Pharmaceutical Sciences, Research Associate, 大学院・薬学研究科, 助手 (20322307)
NAKAMURA Jyunzo  Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (30115901)
SAKAEDA Toshiyuki  Kobe University, School of Medicine, Associate Professor, 医学部附属病院, 助教授 (00304098)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
Keywordsliver / anticancer drug / liver disease / intraperitoneal administration / absorption rate / oharmacokinetics / 抗癌剤
Research Abstract

Development of drug delivery system to achieve site-specific delivery or prolonged retention in the circulation has attracted attention, because new types of drugs are expected to be created with advance in life science and biotechnology such as human genome project. We have tried to develop a new administration route for drug targeting to the liver, since normal drug administration by intravenous and oral route have difficulty in achieving a local site of action in the liver. As an anticancer model drug 5-fluorouracil (5-FU), we examined its hepatic disposition after application to the rat liver surface by employing a diffusion cell, and indicated the possibility for liver targeting. In addition, we suggested the novel application route to the other organ surfaces for genome medicine. Furthermore, we have examined the influence of liver disease on drug absorption from the liver surface membrane regarded as the first barrier for drug targeting to the liver. The main purpose of this study is to examine the possibility of direct liver surface application for drug targeting method. We employed rats intoxicated with carbon tetrachloride (CC14) or D-galactosamine (GAL) as the liver disease model, and examined drug absorption characteristics after application to the liver surface, by utilizing a cylindrical diffusion cell. In the liver-intoxicated rats, about 90 % of a low molecular weight drug phenolsulfonphthalein (PSP) as a model was absorbed from the liver surface in 6 h, similar to the normal rats (no treatment). Although the absorption rate was increased in the CC14 group whereas slightly retarded absorption was observed in GAL group, there should be no serious problem for clinical use of liver surface application. Consequently, it is expected that no marked decline in the absorption rate from liver surface in liver disease state and liver resection, leading to apply this administration method for liver targeting.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Koyo Nishida: "Absorption characteristics of model compounds with different molecular weights from the serosal caecal surface in rats"Journal of Pharmacy and Pharmacology. 54・7. 1005-1009 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Koyo Nishida: "Influence of liver disease on phenolsulfonphthalein absorption from liver surface to examine possibility of direct liver surface application for drug targeting"Biological & Pharmaceutical Bulletin. 26・7. 988-993 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Koyo Nishida: "Development of drug delivery system based on a new administration route for targeting to the specific region in the liver"YAKUGAKU ZASSHI. 123・8. 681-689 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Koyo Nishida: "Absorption of phenolsulfonphthalein as a model across the mesenteric surface in rats to determine the drug absorption route after intraperitoneal administration"Journal of Pharmacy and Pharmacology. 56(印刷中). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Koyo Nishida: "Absorption characteristics of compounds with different molecular weights after application to the unilateral kidney surface in rats"European Journal of Pharmaceutics and Biopharmaceutics. 57(印刷中). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Koyo Nishida: "Absorption characteristics of model compounds with different molecular weights from the serosal caecal surface in rats"Journal of Pharmacy and Pharmacology. 54-7. 1005-1009 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Koyo Nishida: "Influence of liver disease on phenolsulfonphthalein absorption from liver surface to examine possibility of direct liver surface application for drug targeting"Biological & Pharmaceutical Bulletin. 26-7. 988-993 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Koyo Nishida: "Development of drug delivery system based on a new administration route for targeting to the specific region in the liver"YAKUGAKU ZASSHI. 1232-8. 681-689 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Koyo Nishida: "Absorption of phenolsulfonphthalein as a model across the mesenteric surface in rats to determine the drug absorption route after intraneritoneal administration"Journal of Pharmacy and Pharmacology. 56(in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Koyo Nishida: "Absorption characteristics of compounds with different molecular weights after application to the unilateral kidney surface in rats"European Journal of Pharmaceutics and Biopharmaceutics. 57(in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Koyo Nishida: "Influence of liver disease on phenolsulfonphthalein absorption from liver surface to examine possibility of direct liver surface application for drug targeting"Biological & Pharmaceutical Bulletin. 26・7. 988-993 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Koyo Nishida: "Development of drug delivery system based on a new administration route for targeting to the specific region in the liver"YAKUGAKU ZASSHI. 123・8. 681-689 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Koyo Nishida: "Absorption characteristics of model compounds with different molecular weights from the serosal caecal surface in rats"Journal of Pharmacy and Pharmacology. 54・7. 1005-1009 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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