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Research and development of innovative cardioprotective modality by nanoparticle-mediated targeting to inflammatory monocytes and IR myocardium

Research Project

Project/Area Number 25293185
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionKyushu University

Principal Investigator

Egashira Kensuke  九州大学, 学内共同利用施設等, 教授 (60260379)

Co-Investigator(Renkei-kenkyūsha) MATOBA Tetsuya  九州大学病院, 循環器内科, 講師 (20448426)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2013: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Keywords虚血再灌流傷害 / 急性心筋梗塞 / 再灌流療法 / ナノテクノロジー / ドラッグ・デリバリー・システム
Outline of Final Research Achievements

In rat and pig IR models, poly(lactic acid/glycolic acid) (PLGA) nanoparticle incorporating FITC accumulated in the IR myocardium through enhanced vascular permeability, and in CD11b-positive leukocytes in the IR myocardium and peripheral blood after intravenous treatment. Intravenous treatment with PLGA nanoparticle containing pitavastatin (Pitavastatin-NP, 1 mg/kg) at reperfusion reduced MI size after 24 hours and ameliorated left ventricular dysfunction 4-week after reperfusion; by contrast, pitavastatin alone (as high as 10 mg/kg) showed no therapeutic effects.
In mouse model IR model, treatment with nanoparticles incorporated with CsA (CsA-NP) pioglitazone, irbesartan and etc at the onset of reperfusion enhanced cardioprotection against IR injury by those drugs alone.
Therefore, this nanotechnology-based platform can be developed as an innovative cardioprotective modality that may advance currently unsatisfactory reperfusion therapy for AMI.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (24 results)

All 2016 2015 2014 2013 Other

All Journal Article (7 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (14 results) (of which Invited: 9 results) Remarks (3 results)

  • [Journal Article] Nanoparticle-Mediated Targeting of Cyclosporine A Enhances Cardioprotection Against Ischemia-Reperfusion Injury Through Inhibition of Mitochondrial Permeability Transition Pore Opening.2016

    • Author(s)
      Ikeda G, Matoba T, Nakano Y, Nagaoka K, Ishikita A, Nakano K, Funamoto D, Sunagawa K, Egashira K.
    • Journal Title

      Sci Rep.

      Volume: 6 Issue: 1 Pages: 20467-20467

    • DOI

      10.1038/srep20467

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A New Therapeutic Modality for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin Induces Cardioprotection from Ischemia-Reperfusion Injury via Activation of PI3K/Akt Pathway and Anti-Inflammation in a Rat Model.2015

    • Author(s)
      Nagaoka K, Matoba T, Mao Y, Nakano Y, Ikeda G, Egusa S, Tokutome M, Nagahama R, Nakano K, Sunagawa K, Egashira K.
    • Journal Title

      PLoS One.

      Volume: 10(7) Issue: 7 Pages: e0132451-e0132451

    • DOI

      10.1371/journal.pone.0132451

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nanoparticle-mediated drug delivery system for cardiovascular disease.2014

    • Author(s)
      Matoba T, Egashira K
    • Journal Title

      Int Heart J.

      Volume: 55(4) Pages: 281-286

    • NAID

      130004941279

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nanoparticle-mediated delivery of pitavastatin inhibits atherosclerotic plaque destabilization/rupture in mice by regulating the recruitment of inflammatory monocytes.2014

    • Author(s)
      Katsuki S, Matoba T, Nakashiro S, Sato K, Koga J, Nakano K, Nakano Y, Egusa S, Sunagawa K, Egashira K.
    • Journal Title

      Circulation.

      Volume: 129 Issue: 8 Pages: 896-906

    • DOI

      10.1161/circulationaha.113.002870

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mouse models of plaque rupture.2013

    • Author(s)
      Matoba T, Sato K, Egashira K
    • Journal Title

      Curr Opin Lipidol.

      Volume: 24 Issue: 5 Pages: 419-425

    • DOI

      10.1097/mol.0b013e3283646e4d

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] シーズ成果報告〈医薬品〉急性心筋梗塞症治療用ナノ粒子製剤の実用化のための橋渡し研究2013

    • Author(s)
      江頭健輔、中野覚、松本拓也、前原喜彦
    • Journal Title

      臨床評価

      Volume: 41(1) Pages: 68-71

    • Related Report
      2013 Annual Research Report
  • [Journal Article] シーズ成果報告〈医薬品〉虚血肢治療用低侵襲ナノ粒子製剤の実用化2013

    • Author(s)
      江頭健輔、中野覚、松本拓也、前原喜彦
    • Journal Title

      臨床評価

      Volume: 41(1) Pages: 72-74

    • Related Report
      2013 Annual Research Report
  • [Presentation] 未解決の難治性心血管病に対する革新的ナノ医療の実用化臨床試験(出口を見据えた研究開発)2015

    • Author(s)
      江頭健輔
    • Organizer
      第38回日本バイオレオロジー学会年会
    • Place of Presentation
      東京
    • Year and Date
      2015-06-06
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Nanoparticles-Mediated Delivery of Pioglitazone Reduces Myocardial Ischemia-Reperfusion Injury by Antagonizing Monocyte-mediated Inflammation in Preclinical Animal Models2014

    • Author(s)
      Tokutome M, Matoba T, Nakano Y, Nakano K, Sunagawa K, Egashira K
    • Organizer
      Scientific Sessions 2014 of the American Heart Association
    • Place of Presentation
      Chicago
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Nanoparticle-Mediated Delivery of Pitavastatin into Small Pulmonary Arteies by Intravenous Administration Attenuated the Progression of Already Established Monocrotaline-induced Pulmonary Arterial Hypertension in Rats2014

    • Author(s)
      Ichimura K, Matoba T, Nagahama R, Nakano K, Sunagawa K, Egashira K
    • Organizer
      Scientific Sessions 2014 of the American Heart Association
    • Place of Presentation
      Chicago
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Nanoparticle-Mediated Targeting of a Mitochondria Division Inhibitor, Mdivi-1, to the Mitochondria Induces Cardioprotection from Ischemia-Reperfusion Injury2014

    • Author(s)
      Ishikita A, Matoba T, Ikeda G, Mao Y, Nakano K, Sunagawa K, Egashira K
    • Organizer
      Scientific Sessions 2014 of the American Heart Association
    • Place of Presentation
      Chicago
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Nanoparticle-Mediated Simultaneous Targeting to Mitochondria and Inflammatory Monocytes Confers Additive Cardioprotection Against Myocardial Ischemia-Reperfusion Injury2014

    • Author(s)
      Ikeda G, Matoba T, Nakano K, Sunagawa K, Egashira K
    • Organizer
      Scientific Sessions 2014 of the American Heart Association
    • Place of Presentation
      Chicago
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Nanoparticle-mediated targeting of pitavastatin for developing innovative therapeutic strategies in refractory cardiovascular diseases.2014

    • Author(s)
      Egashira K
    • Organizer
      The Annual Scientific Meeting of Taiwan Society of Lipids & Atherosclerosis 2014 and The 14th Taipei International Vascular Biology Symposium
    • Place of Presentation
      Taipei
    • Year and Date
      2014-09-14 – 2014-09-15
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Nanoparticle-mediated Targeting of Pitavastatin for Developing Innovative Therapeutic Strategies in Refractory Cardiovascular Diseases2014

    • Author(s)
      Egashira K
    • Organizer
      The 18th International Vascular Biology Meeting
    • Place of Presentation
      Kyoto
    • Year and Date
      2014-04-14 – 2014-04-17
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Targeting of Pitavastatin into Reperfused Myocardium Reduces Ischemia-Reperfusion Injury in a Preclinical Porcine Model2014

    • Author(s)
      Ichimura K, Nakano K, Nagaoka K, Matoba T, Egusa S, Sunagawa K, Egashira K
    • Organizer
      The 18th International Vascular Biology Meeting
    • Place of Presentation
      Kyoto
    • Year and Date
      2014-04-14 – 2014-04-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] 臨床ニーズに基づく低侵襲医療機器開発と産学連携2014

    • Author(s)
      江頭健輔
    • Organizer
      第8回医療機器産業研究会 新たな医療機器開発の方向性と産業戦略
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 難治性心血管病に対する革新的ナノ医療の実用化と臨床試験2013

    • Author(s)
      江頭健輔
    • Organizer
      先端医療研究セミナー
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 血管選択的DDSナノ粒子製剤の開発による重症虚血肢に対する治療的血管新生の実用化2013

    • Author(s)
      江頭健輔
    • Organizer
      第113回日本外科学会定期学術集会
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 難治性心血管病に対する革新的ナノ医療の実用化と臨床試験2013

    • Author(s)
      江頭健輔
    • Organizer
      第4回「新しい医療」講演会
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Nanoparticle-mediated targeting of pitavastatin for developing innovative therapeutic strategies in refractory cardiovascular diseases.2013

    • Author(s)
      Egashira K
    • Organizer
      The Annual Scientific Meeting of Taiwan Society of Lipids & Atherosclerosis 2013
    • Place of Presentation
      Taipei
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 難治性心血管病に対する革新的ナノ医療の実用化と臨床試験2013

    • Author(s)
      江頭健輔
    • Organizer
      榊原記念病院定例講演会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Remarks] 循環器病未来医療研究センター・循環器病先端医療研究開発学部門

    • URL

      http://www.med.kyushu-u.ac.jp/cardiol/1_sentaniryo/

    • Related Report
      2015 Annual Research Report
  • [Remarks] 循環器病先端医療研究開発学講座

    • URL

      http://www.med.kyushu-u.ac.jp/cardiol/1_sentaniryo/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 循環器病先端医療研究開発学講座

    • URL

      http://www.med.kyushu-u.ac.jp/cardiol/1_sentaniryo/

    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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