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Development of a novel DDS targeting ischemic stroke region by using leukocyte-like function and control of brain microenvironment via faint electricity

Research Project

Project/Area Number 17H06906
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Physical pharmacy
Research InstitutionThe University of Tokushima

Principal Investigator

FUKUTA Tatsuya  徳島大学, 大学院医歯薬学研究部(薬学域), 助教 (90805160)

Project Period (FY) 2017-08-25 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords脳梗塞 / 血液脳関門 / リポソーム / 白血球 / 膜タンパク質 / 脂質膜間移行 / 炎症血管内皮 / 微弱電流 / DDS / 細胞間接着 / 脂質膜間移行現象
Outline of Final Research Achievements

We previously demonstrated that drug delivery with nano-sized liposomes is available for the treatment of ischemic stroke via passage through the disintegrated blood-brain barrier (BBB) after a stroke. However, liposomal entry into the brain parenchyma was limited at an early phase following ischemia/reperfusion. As leukocytes can pass through the BBB regardless of such conditions via utilizing the functions of their membrane proteins, we hypothesized that incorporation of leukocyte membrane proteins onto liposomal membranes may impart leukocyte-mimicking functions to liposomes. In this research, we developed leukocyte-mimetic liposomes (LM-Lipo) by leukocyte membrane protein transfer and evaluated their function in vitro. The results suggested that transfer of leukocyte membrane proteins onto liposomes could allow for association of the liposomes with inflamed endothelial cells, and subsequent passage through the inflamed endothelial cell layer via change of intercellular junctions.

Academic Significance and Societal Importance of the Research Achievements

学術的な意義として、本研究成果がさらに発展し、白血球が有する生体機能を模倣したリポソームを構築することで、ナノ粒子を用いた脳梗塞治療が抱える課題を解決し、脳への薬物送達の最大の障壁である血液脳関門を突破可能な新規薬物送達システム(DDS)の開発に繋がり得る点が挙げられる。社会的意義として、脳梗塞に対する新たな治療薬の開発に貢献でき、患者QOLの向上と、超高齢社会で問題とされる要介護人口の減少と医療経済の改善に繋がることが期待される。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report

Research Products

(9 results)

All 2019 2018

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Leukocyte-mimetic liposomes possessing leukocyte membrane proteins pass through inflamed endothelial cell layer by regulating intercellular junctions.2019

    • Author(s)
      Fukuta T, Yoshimi S, Tanaka T, Kogure K.
    • Journal Title

      International Journal of Pharmaceutics

      Volume: 563 Pages: 314-323

    • DOI

      10.1016/j.ijpharm.2019.04.027

    • NAID

      120006845651

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Applications of Liposomal Drug Delivery Systems to Develop Neuroprotective Agents for the Treatment of Ischemic Stroke2019

    • Author(s)
      Fukuta T, Ishii T, Asai T, Oku N.
    • Journal Title

      Biol. Pharm. Bull.

      Volume: 42 Issue: 3 Pages: 319-326

    • DOI

      10.1248/bpb.b18-00683

    • NAID

      130007606450

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 脳梗塞部位の血液脳関門の能動的突破を目指したDDS開発2019

    • Author(s)
      福田達也,小暮健太朗
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] がん親和性付与を目的とした単球膜タンパク質搭載リポソームの構築2019

    • Author(s)
      吉見真太朗,福田達也,田中 保,小暮健太朗
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脳梗塞部位の血液脳関門突破を目指した白血球模倣ナノ粒子の開発2019

    • Author(s)
      福田達也, 小暮健太朗
    • Organizer
      日本膜学会第41年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 炎症血管バリアの突破を目指した白血球模倣リポソームの構築2019

    • Author(s)
      福田達也, 吉見真太朗, 小暮健太朗
    • Organizer
      日本薬剤学会第34年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脂質膜間移行現象を利用したリポソームへの白血球様機能の付与2018

    • Author(s)
      福田達也, 田中 保, 小暮健太朗
    • Organizer
      日本膜学会第40年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 微弱電流による特殊なエンドサイトーシスを利用した高分子送達の機構解析2018

    • Author(s)
      福田達也, 虎尾 祐, 三村美夕紀, 大島康史, 中谷奈津, 田中 保, 小暮健太朗.
    • Organizer
      第18回遺伝子・デリバリー研究会第18回夏期セミナー
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of liposomes with leukocyte-like function by intermembrane transfer of leukocyte membrane proteins.2018

    • Author(s)
      Fukuta T, Tanaka T, Kogure K.
    • Organizer
      18th Symposium for Gene・Design and Delivery
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research

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Published: 2017-08-25   Modified: 2020-03-30  

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