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Development of pulmonary fibrosis drug based on lung-targeting and long-acting nano-DDS

Research Project

Project/Area Number 17K08449
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionNagasaki University

Principal Investigator

KODAMA Yukinobu  長崎大学, 病院(医学系), 准教授 (50448510)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords遺伝子デリバリー / 肺線維症 / 遺伝子・核酸医薬 / ナノ粒子 / ドラッグデリバリー / 核酸医薬 / 肺指向性 / 核酸 / 薬学
Outline of Final Research Achievements

In this study, we developed gene and nucleic acid medicines for lung fibrosis based on lung-targeted nanoparticles. Nanoparticles could be constructed by optimizing the mixing ratio of pDNA, cationic polymer, and anionic polymer for self-assembly. Nanoparticles showed high gene expression in lung fibroblasts cell lines. In addition, High gene expression was selectively shown in the lung after intravenous administration, Furthermore, the nanoparticles were also able to adapt to siRNA. As a result of adding nanoparticles containing pDNA encoding HGF to lung fibroblasts, it was shown that they were taken up by lung fibroblasts and express and secrete HGF. Furthermore, although it was a preliminary study, as a result of administration to pulmonary fibrosis model mice, the survival rate tended to be prolonged as compared with the control.

Academic Significance and Societal Importance of the Research Achievements

本研究により、肺に選択的に送達できるナノ微粒子の調製に成功した。このナノ微粒子は肺線維芽細胞に良好に取り込まれ、遺伝子発現することができるため、肺線維症に対する遺伝子・核酸医薬開発へ応用することが可能である。未だに満足いく治療薬がない疾患である肺線維症治療薬に寄与することができると考えている。さらに、他の肺疾患にも応用が可能であるため、幅広く医療貢献ができる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (11 results)

All 2019 2018 2017

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (8 results) (of which Invited: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Methotrexate-Coated Complexes of Plasmid DNA and Polyethylenimine for Gene Delivery2018

    • Author(s)
      Kodama Y, Nishigaki W, Nakamura T, Fumoto S, Nishida K, Kurosaki T, Nakagawa H, Kitahara T, Muro T, Sasaki H.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 41 Issue: 10 Pages: 1537-1542

    • DOI

      10.1248/bpb.b18-00144

    • NAID

      130007494219

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2018-10-01
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Gene delivery system of pDNA using the blood glycoprotein fetuin.2018

    • Author(s)
      Kodama Y, Hanamura H, Muro T, Nakagawa H, Kurosaki T, Nakamura T, Kitahara T, Kawakami S, Nakashima M, Sasaki H.
    • Journal Title

      Journal of Drug Targeting

      Volume: 印刷中 Issue: 7 Pages: 604-609

    • DOI

      10.1080/1061186x.2017.1405425

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 静電的相互作用を基盤としたaptamer被膜型遺伝子ベクターの開発2019

    • Author(s)
      黒崎 友亮、兒玉 幸修、中川 博雄、中村 忠博、大山 要、中嶋 幹郎、川上 茂、佐々木 均
    • Organizer
      日本薬剤学会第34年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 生体適合性素材の自己組織化による標的化DDS製剤の開発2019

    • Author(s)
      兒玉 幸修
    • Organizer
      日本薬剤学会第34年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 大腸がん腹膜播種に対するMDM2-siRNA複合体の有効性評価2018

    • Author(s)
      丸田 由佳理, 兒玉 幸修, 北原 隆志, 佐々木 均
    • Organizer
      日本薬剤学会第33年会
    • Related Report
      2018 Research-status Report
  • [Presentation] c-Myc-siRNA三重複合体によるメラノーマ増殖抑制に関する基礎的検討2018

    • Author(s)
      三枝 由香莉, 兒玉 幸修, 北原 隆志, 佐々木 均
    • Organizer
      日本薬剤学会第33年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 大腸がん腹膜播種に対するVEGF-siRNAナノ粒子の開発2018

    • Author(s)
      大倉 真生, 兒玉 幸修, 北原 隆志, 佐々木 均
    • Organizer
      第34回日本DDS学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 生体分解型siRNAベクターの構築と有用性評価2018

    • Author(s)
      柿木 優希, 佐々木 均, 北原 隆志, 兒玉 幸修
    • Organizer
      第34回日本DDS学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] VEGF-siRNA複合体によるメラノーマ肺転移の抑制2018

    • Author(s)
      岡田 明莉, 兒玉 幸修, 加藤 由佳, 北原 隆志, 佐々木 均
    • Organizer
      第34回日本DDS学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] メラノーマに対する生体分解型VEGF-siRNA複合体の有用性評価2017

    • Author(s)
      加藤 由佳、兒玉 幸修、上田 由貴、北原 隆志、佐々木 均
    • Organizer
      日本薬剤学会第32年会
    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 肺指向性薬物送達体2019

    • Inventor(s)
      佐々木 均、兒玉 幸修、川上 茂
    • Industrial Property Rights Holder
      佐々木 均、兒玉 幸修、川上 茂
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-098677
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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