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Development of intracellular controlled release system for optimization of gene therapy

Research Project

Project/Area Number 13470515
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionOsaka University

Principal Investigator

MAYUMI Tadanori  Osaka University, Graduate School of Pharmaceutical Sciences, Professor, 薬学研究科, 教授 (00098485)

Co-Investigator(Kenkyū-buntansha) TSUTSUMI Yasuo  Osaka University, Graduate School of Pharmaceutical Sciences, Research Associate, 薬学研究科, 助手 (50263306)
NAKAGAWA Shinsaku  Osaka University, Graduate School of Pharmaceutical Sciences, Associate Professor, 薬学研究科, 助教授 (70207728)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2003: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2001: ¥5,000,000 (Direct Cost: ¥5,000,000)
Keywordsintracellular controlled release / nanoparticles / fusogenic liposomes / drug delivery system / oligonucleotide / confocal laser microscope / gene therapy / ナノパーティクル / 細胞内徐放 / 細胞内導入 / FACS / ナノスフェアー / アンチセンス核酸 / 薬物動態 / ポリビニルアミン
Research Abstract

In recent years, sustained or controlled drug-release system using nanospheres or microspheres is noticed in systemic pharmacokinetics. However, in the near future, not only "systemic pharmacokinetics" but also "intracellular pharmacokinetics seems to be important in Drug Delivery System research. Technology for delivering sustained release particles such as nanospheres into cytoplasm is indispensable to control the intracellular pharmacokinetics. Although some systems have been already achieved to deliver soluble drugs into cytoplasm, no system has been successful in delivering nanoparticles into cytoplasm for further sustained regulation of drug release in intracellular compartments. In this study, we established a protocol to encapsulate nanoparticles into liposomes. Additionally, the, liposomes were fur.ther fused with ultraviolet-inactivated Sendai virus in order to make fusogenic liposomes. We demonstrated that fusogenic liposomes could deliver the encapsulated nanoparticless into cytoplasm via fusion-dependent manner rather thanrendocytosis. Also nanoparticles were introduced in 94% of the 105 cells treated with fusogenic liposomes encapsulating nanoparticles. The mean number of nanoparticles introduced into cytoplasm was about 10 particles / ce11. Additionally, to evaluate intracellular slow release of drugs, nanoparticles that had adsorbed FITC-labeled oligonucleotide was introduced into the cytoplasm by fusogenic liposome. FITC-labeled oligonucleotide was confirmed to be released gradually into the cytoplasm for more than 7 days. We conclude that the technology, which can be used for the encapsulation of any functional nanoparticles, is valuable for regulation of intracellular pharmacokinetics.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] J.Kunisawa: "Sendai virus fusion protein-mediates simultaneous induction of MHC class I/II-dependent mucosal and systemic immune responses via the nasopharyngeal-associated lymphoreticular tissue immune system."J.Immunol.. 167. 1406-1412 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 國澤 純: "粘膜ワクチンの新しい展開"医学のあゆみ. 199. 125-130 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 中川晋作: "遺伝子医薬品のDDS"医薬ジャーナル. 37. 1559-1565 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 國澤 純: "ワクチンにおけるFusogenic liposomeの応用"臨床免疫. 35. 122-126 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 國澤 純: "DDS技術を用いた癌治療 膜融合リポソームの癌治療への応用"癌と化学療法. 28. 577-583 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 林 哲: "DDSの免疫療法:ワクチン開発とDDS"分子がん治療. 2. 197-204 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J.Kunisawa: "Pharmacotherapy by intracellular delivery of drugs using fusogenic liposomes : application to vaccine development."Adv.Drug Del.Rev.. 52. 177-186 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J.Kunisawa: "Lack of antigen-specific immune responses in anti-IL-7 receptor α chain antibody-treated Peyer's path-null mice following intestinal immunization with microencapsulated antigen."Eur.J.Immunol.. 32. 2347-2355 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 真弓忠範: "DDSとナノ粒子 特集によせて"生物工学会誌. 81. 177-177 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 中川晋作: "細胞内薬物動態制御を目指した機能性ナノ粒子の細胞質内導入"生物工学会誌. 81. 189-192 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Nakagawa: "Development of novel technology of DDS for gene therapy."Drug Metabol.Pharmacokin.. 18. 223-229 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] R.Nakano: "A novel T7 system utilizing mRNA coding for T7 RNA polymerase."Biochem.Biophys.Res.Commun.. 301. 974-978 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] A.Hayashi: "Biomedical Polymers and Polymer Therapeutics"Kluwer Academic/Plenum Publishers. 16 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J.Kunisawa, T.Nakanishi, I.Takahashi, A.Okudaira, Y.Tsutsumi, K.Katayama, S.Nakagawa, H.Kiyono, T.Mayumi: "Sendai virus fusion protein-mediates simultaneous induction of MHC class I/II-dependent mucosal and systemic immune responses via the nasopharyngeal-associated lymphoreticular tissue immune system."J.Immunol.. 167. 1406-1412 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J.Kunisawa, T.Nakanishi, I.Takahashi, A.Okudaira, Y.Tsutsumi, K., Katayama, S.Nakagawa, H.Kiyono, T.Mayumi: "New aspects and paradigms for the development of mucosal vaccine."Igakunoayumi. 199. 125-130 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Nakagawa, T.Mayumi: "Drug delivery system for gene medicine."Medicine and Drug Journal. 37. 1559-1565 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J.Kunisawa, S.Imazu, A.Hayashi, H.Kiyono, T.Mayumi: "Application of fusogenic liposome for the antigen delivery system."Clinical immunology. 35. 122-126 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J.Kunisawa, T.Mayumi: "Application of novel drug delivery system, fusogenic liposome,. for cancer therapy."Jpn.J.Cancer Chemother.. 28. 577-583 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] A.Hayashi, J.Kunisawa, Y.Tsutsumi, S.Nakagawa, T.Mayumi: "Drug delivery system for Immunotherapy"Bunshi Gan Chiryou. 2. 197-204 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J.Kunisawa, S.Nakagawa, T.Mayumi: "Pharmacotherapy by intracellular delivery of drugs using fusogenic liposomes: application to vaccine development."Adv.Drug Del.Rev.. 52. 177-186 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] J.Kunisawa, I.Takahashi, A.Okudaira, T.Hiroi, K.Katayama, T.Ariyama, Y.Tsutsumi, S.Nakagawa, H.Kiyono, T.Mayumi: "Lack of antigen-specific_immune responses in anti-IL-77 receptor α chain antibody-treated Peyer's path-null mice following intestinal immunization with microencapsulated antigen."Eur.J.Immunol.. 32. 2347-2355 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] T.Mayumi: "DDS and nanoparticle"Seibutukougakukaishi. 81. 177-177 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Nakagawa, T.Mayumi: "Direct introduction of nanoparticles into cytoplasm of living cells using fusogenic liposomes."Seibutukougakukaishi. 81. 189-192 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Nakagawa, T.Mayumi: "Development of novel technology of DDS for gene therapy."Drug Metabol. Pharmacokin.. 18. 223-229 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] R.Nakano, T.Nakagawa, S.Imazu, K.Katayama, H.Mizuguchi, T.Hayakawa, Y.Tsutsumi, S.Nakagawa, T.Mayumi: "A novel T7 system utilizing mRNA coding for T7 RNA polymerase."Biochem.Biophys.Res.Commun.. 301. 974-978 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] A.Hayashi, T.Mayumi: "Development of fusogenic liposomes and its application for vaccine."Biomed.Polym.Polym.Therap.(New York). 315-330 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 中川晋作: "細胞内薬物動態制御を目指した機能性ナノ粒子の細胞質内導入"生物工学会誌. 81. 189-192 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] S.Nakagawa: "Development of novel technology of DDS for gene therapy"Drug Metabol.Pharmacokin.. 18. 223-229 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] J.Kunisawa: "Lack of antigen-specific Immune responses in anti-IL-7 receptor a antibody-treated Peyer's patch-null mice following intestinal immunization with microencapsulated antigen"Eur. J. Immunol.. 32. 2347-2355 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] J.Kunisawa: "Sendai virus fusion protein-mediates simultaneous induction of MHC class I/II-dependent mucosal and systemic immune responses via the nasopharyngeal-associated lymphoreticular tissue immune system"J. Immunol.. 167. 1406-1412 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 中川晋作: "遺伝子医薬品のDDS"医薬ジャーナル. 37. 1559-1565 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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