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1992 Fiscal Year Final Research Report Summary

Development of intracellular drug delivery system utilizing liposomes

Research Project

Project/Area Number 02670981
Research Category

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

Allocation TypeSingle-year Grants
Research Field Physical pharmacy
Research InstitutionUniversity of Tokushima

Principal Investigator

KIWADA Hiroshi  Univ.Tokushima,Facul.Pharm.Sci.,Professor, 薬学部, 教授 (50120184)

Co-Investigator(Kenkyū-buntansha) SUGIYAMA Yuichi  Univ.Tokyo,Facul.Pharm.Sci.,Professor, 薬学部, 教授 (80090471)
HARASHIMA Hideyoshi  Univ.Tokushima,Facul.Pharm.Sci.,Assoc.Professor, 薬学部, 助教授 (00183567)
Project Period (FY) 1990 – 1992
KeywordsDrug delivery system / Liposome / Macrophage / Lysosome / Opsonin / Complement receptor / Pharmacokinetics
Research Abstract

The usefulness of liposomes as drug carriers has been widely studied in the world, especially on the uptake mechanism by the liver. However,very few studies on the intracellular fate of internalized liposomes have been reported under the common understanding that they are transferred to lysosomes and degradated there. Control of the intracellular fate such as escape of transfer to lysosome and degradation has never been attempted. It is very important to consider the intracellular fate of liposomes after internalization for the development of useful drug delivery system utilizing liposomes as well as the targetability after intravenous injection.
This research was carried out to elucidate the intracellular fate of liposomes and following results were obtained: (1)Perfusion study using rat liver revealed that liposomes were opsonized by plasma protein depending on their particle size. (2)By infusion study,it was found that the saturation process of liver uptake was not expressed by conventional Michaelis-Menten kinetics but by novel kinetic model in which the uptake clearance was decreased by increasing accumulated amount of liposomes in the liver,not by blood concentration. (3)It became apparent that liposomes modified with cetylmannoside were not taken up by kupffer cells via mannose receptor on the cells surface as commonly expected,and the contribution of complement receptors was suggested on the uptake. (4)The method for quantitative estimation of degradation process in lysosomes was presented,and the pharmacokinetic analysis of the data obtained from in vivo and in vitro experiments by this methods made it possible to evaluate the degradation process in the cells quantitatively.
Findings obtained in this study are considered to give very useful informations for development of liposomal drug carriers. As next step of the research,the relationship between internalization process and intracellular fate of liposomes will be focussed.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Kouichi Funato et al.: "Contribution of complement system on destabilization of liposomes composed of hydrogenated egg phosphatidylcholine in rat fresh plasma" Biochim.Biophys.Acta. 1103. 198-204 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hideyoshi Harashima et al.: "Non-Michaelis-Menten Type Hepatic Uptake of Liposomes in the Rat" J.Pharm.Pharmacol.44. 707-712 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chikamasa Yamashita et al.: "Potential Value of Cetylmannoside Liposomes as Carriers of Macrophage Activators to Human Blood Monocytes" Jpn.J.Cancer Res.82. 569-576 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chikamasa Yamashita et al.: "Emhancing effect of cetylmannoside on targeting of liposomes to Kupffer cells in rats" Int.J.Pharm.70. 225-233 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshihiro Kume et al.: "Saturable,Non-Michaelis-Menten Uptake of Liposomes by the Reticuloendothelial System" J.Pharm.Pharmacol.43. 162-166 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hideki Tsuji et al.: "Targeting of Liposomes Surface-Modified with Glycyrrhizin to the liver.I.Preparation and Biological Disposition" Chem.Pharm.Bull.39. 1004-1008 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kouchi Funato et al: "Contribution of complement system on destabilization of liposomes composed of hydrogenated egg phosphatidylcholine in rat fresh plasma" Biochim.Biophys.Acta. 1103. 198-204 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hideyoshi Harashima et al: "Non-Michaelis-Menten Type Hepatic Uptake of Liposomes in the Rat" J.Pharm.Pharmacol. 44. 707-712 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chikamasa Yamashita et al: "Potential Value of Cetylmannoside Liposomes as Carriers of Macrophage Activators to Human Blood Monocytes" Jpn.J.Cancer Res. 82. 569-576 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chikamasa Yamashita et al: "Emhancing effect of cetylmannoside on targeting of liposomes to kupffer cells in rats" Int.J.Pharm. 70. 225-233 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshihiro Kume et al: "Saturable,Non-Michaelis-Menten Uptake of Liposomes by the Reticuloendothelial System" J.Pharm.Pharmacol. 43. 162-166 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hideki Tsuji et al: "Targeting of Liposomes Surface-Modified with Glycyrrhizin to the liver.I.Preparation and Biological Disposition" Chem.Pharm.Bull. 39. 1004-1008 (1991)

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

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Published: 1994-03-24  

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