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1994 Fiscal Year Final Research Report Summary

Design of Cyclodextrin Derivatives as Artificial Lipid Carriers that are not Receptor-directed

Research Project

Project/Area Number 05671873
Research Category

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

Allocation TypeSingle-year Grants
Research Field 医薬分子機能学
Research InstitutionKumamoto University

Principal Investigator

IRIE Tetsumi  PH.D.Faculty of Pharmaceutical Sciences, Kumamoto University, Department of Pharmaceutics, Research Associate, 薬学部, 助手 (60150546)

Project Period (FY) 1993 – 1994
KeywordsAtherosclerosis / Deposition of Lipids / Cholesterol / Cvclodextrin / Inclusion complex / Retentative in circulation / Site-directed / Sulfate
Research Abstract

Atherosclerosis involves deposits of excessive cholesterol and its esters mainly in the vascular system. On the cellular level, this excessive deposition is result of receptor-regulated uptake of oxidized forms of low-density lipoproteins. It may be possible to correct this situation by introducing into the circulation an alternate lipid carrier that woudd not be receptor directed and that would distribute lipids wore evenly. The objective of this study, therefore, is to investigate the potential use of sulfated cyclodextrins as artificial carriers for atherogenic lipids in a non-receptor mediated manner. The results obtained were as hollows.
1. Sulfoalkylated cyclodextrins enhanced the aqueous solubility of cholesterol and its esters though inclusion complexation, while sulfated cyclodextrins, which have the electric charges located near the cavity, were less effective.
2. Electrophoretic and gel permeation chromatographic studies revealed that the sulfated cyclodextrins showed a selective reactivity toward chyromicron and very-low-density lipoprotein fractions, leading to their aggregation to macroparticles.
3. The intravenous administration of the sulfated cyclodextrins was well tolerated in rats without conspicuous changes in blood chemistry values. Furthermore, the in-vitro hemolytic activity and local tissue irritancy of the sulfated cyclodextrins were much less than those of the parent and their hydrophilic derivatives.
4. Repeated intravenous administration of the sulfated cyclodextrins to hereditary hyperlipidemic rabbits led to a gradual increase in total cholesterol in circulation and eventually to a relief of atherosclerotic lesions in the thoracic aorta.
The intravenous administration of the sulfated cyclodextrins may be used in catalysis of distribution of lipids in organisms and in invasive procedures such as angioplasty, when lipids debris may be released into the blood stream.

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Kazuhiro Fukunaga: "Aluminium β-Cyclodextrin Sulphate as a Stabilizer and Sustained-release Carrier for Basic Fibroblast Growth Factor" Journal of Pharmacy & Pharmacology. 46. 168-171 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazutaka Matsubara: "Controlled Release of the LHRH Agonist Buserelin Acetate from lnjectable Suspensions Containing Triacetylated Cyclodextrins in an Oil Vehicle" Journal of Controlled Release. 31. 173-180 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazufumi Shiotani: "Characterization of the lnclusion Mode of β-Cyclodextrin Sulfate and lts Effect on the Chlorpromazine-induced Hemolysis of Rabbit Erythrocytes" Chemical & Pharmaceutical Bulletin. 42. 2332-2337 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazufumi Shiotani: "Differential Effects of Sulfate and Sulfobutyl Ether of β-Cyclodextrin on Erythrocyte Membranes in Vitro" Pharmaceutical Research. 12. 77-83 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazufumi Shiotani: "Cyclodextrin Sulfates in Parenteral Use:Protection against Gentamicin Nephrotoxicity in the Rat" European Journal of Pharmaceutical Sciences. 3(印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiroyuki Sugiuchi: "Direct Measurement of High-density Lipoprotein Cholesterol in Serum with a Combination of Polyethylene Glycol-modified Enzymes and Sulfated α-Cyclodextrin" Clinical Chemistry. 41(印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kaneto Uekama: "Application of Cyclodextrins.in:A.G.Boer(Ed.),Drug Absorption Enhancement:Concepts,Possibilities and Limitations" Harwood Publishers, 45 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kaneto Uekama: "Pharmaceutical Use of Cyclodextrins in Various Drug Formulations.in:J.-M.Lehn(Ed.),Comprehensive Supermolecular Chemistry" Pergamon Press(印刷中), (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazuhiro Fukunaga: "Aluminium beta-Cyclodextrin Sulphate as a Stabilizer and Sustained-release Carrier for Basic Fibroblast Growth Factor" Journal of Pharmacy & Pharmacology. 46 (3). 168-171 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kazutake Matsubara: "Controlled Release of the LHRH Agonist Buserelin Acetate from Injectable Suspensions Containing Triacetylated Cyclodextrins in an Oil Vehicle" Journal of Controlled Release. 31 (2). 173-180 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kazufumi Shiotani: "Characterization of the Inclusion Mode of beta-Cyclodextrin Sulfate and Its Effect on the Chlorpromazine-induced Hemolysis of Rabbit Erythrocytes" Chemical & Pharmaceutical Bulletin. 42 (11). 2332-2337 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kazufumi Shiotani: "Differential Effects of Sulfate and Sulfobuty1 Ether of beta-Cyclodextrin on Erythrocyte Membranes in Vitro" Pharmaceutical Research. 12 (1). 77-83 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kazufumi Shiotani: "Cyclodextrin Sulfates in Parenteral Use : Protection against Gentamicin Nephrotoxicity in the Rat" European Journal of Pharmaceutical Sciences. 3 (inpress). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroyuki Sugiuchi: "Direct Measurement of High-density Lipoprotein Cholesterol in Serum with a Combination of Polyethylene Glycol modified Enzymes and Sulfated a-Cyclodextrin" Clinical Chemistry. 41 (in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kaneto Uekama: Application of Cyclodextrins.in : A.G.Boer (Ed.), Drug Absorption Enhancement : Concepts, Possibilities and Limitations. Harwood Publishers, 45 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kaneto Uekama: Pharmaceutical Use of Cyclodextrins in Various Drug Formulations.in : J.-M.Lehn (Ed.), Comprehensive Supermolecular Chemistry. Pergamon Press (in press), (1995)

    • 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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