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Freeze-Drying and Stabilization of Liposomes Encapsulating Drug and Enzyme

Research Project

Project/Area Number 60571022
Research Category

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

Allocation TypeSingle-year Grants
Research Field Physical pharmacy
Research InstitutionGifu Pharmaceutical University

Principal Investigator

HANDA Tetsurou  Gifu Pharmaceutical University ・ Associate Professor, 薬学部, 講師 (00025719)

Co-Investigator(Kenkyū-buntansha) TAKEUCHI Hirofumi  Gifu Pharmaceutical University ・ Instructor, 薬学部, 助手 (50171616)
KAWASHIMA Yoshiaki  Gifu Pharmaceutical University ・ Professor, 薬学部, 教授 (30082978)
Project Period (FY) 1985 – 1986
Project Status Completed (Fiscal Year 1986)
Budget Amount *help
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1986: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1985: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsLyophilization of Liposomes / Size Control of Liposomes / Fluidity of Liposomes / Modified REV Method / Freeze-Thawing of Liposomes / 蛋白のリポソームへの内包
Research Abstract

Liposomes have been considered to have great potential as drug delivery vehicles. From pharmaceutical stand-point, the chemical and physical stabilities of "liposome particles" are critically important parameters affecting the performance of drug loaded liposomes in vivo. Lyophilization and size control of liposomes encapsulating drug or enzyme protein are investigated to improve the liposome stabilities.
1. A modification of the reversed-phase evaporation method (modified REV method) was developed for the preparation of lyophilized liposomes. The encapsulation efficiencyies of liposomes after a dehydration(lyophilization)-rehydration procedure were satisfactory high, and the liposome sizes were maintained nearly constant throughout the procedure. These results are different from those obtained with liposome samples prepared by the reversed-phase evaporation method. In the latter case, marked enlargement of liposome size and extensive leakage from liposomes were obtained. The small amou … More nt of residual ether in the modified REV liposomes keeps the lipid membranes fluid even at freezing temperature. The fluidity is considered to play an important role in the protection of liposomes against aggregation, fusion and leakage.
2. One step size control of large multi-lamellar liposomes(LMLV) were accomplished by the reconstitution of liposomes through polycarbonate filter with homogeneous pores of 0.6 <mu> m. Pressure difference across the filter was, at most, 1 atom. Size control of LMLV composed of phosphatidylcholine(PC) were well completed when the membrane was in liquid crystalline state. For PC mixtures, at least a part of sections in membrane required to be in liquid crystalline state. Addition of cholesterol into PC membrane in gel state improve the size control, while cholesterol gave negative effects on the reconstitution of membrane in liquid crystalline state. Various hydrophilic compounds, dyes and proteins, were encapsulated in liposomes by the freeze-thawing method. Size control of the resultant LMLV by the reconstitution with polycarbonate filter did not introduced any leakages of encapsulated material. Therefore, it was presumed that the reconstitution of LMLV to the smaller liposomes was performed by tearing off of liquid crystalline section of membrane of LMLV. Less

Report

(1 results)
  • 1986 Final Research Report Summary
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] 半田哲郎: 製薬工場. 6. 776-779 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] 半田哲郎: Che.Pharm.Bull.35. 748-755 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] 半田哲郎: J.Am.Chem.Soc.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] 半田哲郎: 日本化学会誌.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Tetsurou Handa: "Freeze-Drying of Liposomes" Seiyaku Koujou. 6. 776-779 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Tetsurou Handa: "Lyophilized Liposomes Prepared by a Modified Reversed-Phase Evaporation Method" Chem.Pharm. Bull.,. 35. 748-755 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Tetsurou Handa: "Reactivity of Singlet Oxygen Generated by the Photo-Sensitization of Tetraphenylporphyrin in Liposomes" J.Am.Chem.Soc.,.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Tetsurou Handa: "Effects of gel-Liquid Crystalline Phase Transition and Cholesterol on Size Control of Liposomes" J.Chem.Soc.Jph.,.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary

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Published: 1987-03-31   Modified: 2016-04-21  

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