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Development of safety evaluation system for DDS carrier based on network toxicology

Research Project

Project/Area Number 16H01861
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical engineering assessment
Research InstitutionKyoto University

Principal Investigator

Hashida Mitsuru  京都大学, 薬学研究科, 名誉教授 (20135594)

Co-Investigator(Kenkyū-buntansha) 山下 富義  京都大学, 薬学研究科, 教授 (30243041)
樋口 ゆり子  京都大学, 薬学研究科, 准教授 (40402797)
杉山 直幸  京都大学, 薬学研究科, 准教授 (50545704)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥43,290,000 (Direct Cost: ¥33,300,000、Indirect Cost: ¥9,990,000)
Fiscal Year 2019: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Fiscal Year 2018: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
Fiscal Year 2017: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
Fiscal Year 2016: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Keywords安全性評価 / DDS / 薬物動態学 / ドラッグデリバリーシステム
Outline of Final Research Achievements

In the development of DDS, the molecular mechanism of off-target effects has not been discussed enough. This project aims to establish an evaluation system for DDS based on analytical science, informatics, and genomics/proteomics analysis. Transcriptional factors were selected by analyzing databases of drug-induced liver injury and transcriptional factor binding sites. In addition, three proteins with a significant variation in phosphorylation in the liver after administration of DDS formulation were identified by LC/MS/MS. Based on the combinatory analysis of these data, we established CREB reporter assay system and evaluated DDS formulation by the system.

Academic Significance and Societal Importance of the Research Achievements

DDS開発において、体内動態制御と薬効エンドポイントのみがに注目したされて治療効果製剤機能の有効性の評価が優先がなされてきた。本研究の成果により、高感度・網羅的分析とシミュレーションを活用したによる治療システムの安全性評価に関する研究が進むことにが進展期待できする。また、がんや希少疾患など難治性疾患に対する治療戦略において、患者QOL・安心を考えた安全性保証と標的指向性を兼ね備えたDDS製剤の開発に貢献するものと期待される。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (13 results)

All 2019 2018 2017 2016

All Journal Article (3 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (10 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results)

  • [Journal Article] Evaluation of the Theranostic Potential of Perfluorohexane-Based Acoustic Nanodroplets2019

    • Author(s)
      Abdalkader R, Unga J, Yamashita F, Maruyama K, Hashida M
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 12 Pages: 2038-2044

    • DOI

      10.1248/bpb.b19-00525

    • NAID

      130007754506

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-12-01
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The development of mechanically formed stable nanobubbles intended for sonoporation-mediated gene transfection2017

    • Author(s)
      Abdalkader R, Kawakami S, Unga J, Higuchi Y, Suzuki R, Maruyama K, Yamashita F, Hashida M
    • Journal Title

      Drug Delivery

      Volume: 24 Issue: 1 Pages: 320

    • DOI

      10.1080/10717544.2016.1250139

    • NAID

      120006987449

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ステロイドと転写制御2017

    • Author(s)
      樋口ゆり子
    • Journal Title

      臨床麻酔

      Volume: 41 Pages: 1213-1220

    • Related Report
      2017 Annual Research Report
  • [Presentation] Cell surface modification with ligand molecule for targeted delivery of cell-based medicine2019

    • Author(s)
      Yuriko Higuchi
    • Organizer
      OKINAWA COLLOIDS 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] DDSの進歩と将来像:医薬品・医療機器・再生医療統制品の展開に向けて2018

    • Author(s)
      橋田 充
    • Organizer
      第34回日本DDS学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Bio-distribution characteristics of liposomes bearing structurally simplified sialyl Lewis X2018

    • Author(s)
      Yuuki Yamane,Chanikarn Chantarasrivong, Ryosaku Ohta, Yuriko Higuchi, Mitsuru Hashida, Fumiyoshi Yamashita
    • Organizer
      日本薬物動態学会第33回年会/MDO国際合同学会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 薬物投与技術の進歩と未来の医療2018

    • Author(s)
      橋田 充
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 多階層生体機能モデリング・シミュレーション環境を利用した薬物間相互作用の動的シミュレーション2017

    • Author(s)
      山下富義
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      東北大学川内北キャンパス(宮城)
    • Year and Date
      2017-03-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] Progress in drug administration technology and the future of medicine2017

    • Author(s)
      橋田 充
    • Organizer
      The Cutting Edge in Pharmaceutical Sciences -50 Years of Progress Celebrating Les Benet’s 80th Birthday Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ユビキチン-プロテアソーム系によるリプレッサー分解を利用した新規遺伝子発現制御シス テムの構築2017

    • Author(s)
      〇高見理沙、樋口ゆり子、佐々木明彦、山下富義、橋田 充
    • Organizer
      第33回日本DDS学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Functional Characterization of novel Sialyl Lewix X mimic coated-liposomes targeting to E-selectin2016

    • Author(s)
      Chanikarn Chantarasrivong, Akiharu Ueki, Hiromune Ando, Shinya Nakamura, Isao Nakanishi, Yuriko Higuchi, Fumiyoshi Yamashita, Makoto Kiso, Mitsuru Hashida
    • Organizer
      3rd International Conference on Biomaterials Science in Tokyo
    • Place of Presentation
      東京大学本郷キャンパス(東京)
    • Year and Date
      2016-11-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] Development and evaluation of sialyl lewis X mimic-coated liposomes2016

    • Author(s)
      Chanikarn Chantarasrivong, Akiharu Ueki, Hiromune Ando, Shinya Nakamura, Isao Nakanishi, Yuriko Higuchi, Fumiyoshi Yamashita, Makoto Kiso, Mitsuru Hashida
    • Organizer
      The 1st Workshop Japan-Korea Young Scientists on Pharmaceutics
    • Place of Presentation
      京都教育文化センター(京都)
    • Year and Date
      2016-06-24
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 医療イノベーションを支えるサイエンス2016

    • Author(s)
      橋田 充
    • Organizer
      日本薬剤学会第31年会
    • Place of Presentation
      長良川国際会議場(岐阜)
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2021-02-19  

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