OXN-NP Produce Cardioprotective Effects

• Project/Area Number: 16K10628
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: FUKUSHIMA SATSUKI 国立研究開発法人国立循環器病研究センター, 病院, 医長 (80596867)
• Co-Investigator(Kenkyū-buntansha): 斎藤 俊輔 大阪大学, 医学部附属病院, その他 (30600126) ; 仲村 輝也 大阪大学, 医学系研究科, 講師 (90511626) ; 秦 広樹 大阪大学, 医学系研究科, 特任准教授(常勤) (80638198)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: プロスタサイクリン / ナノパーティクル / 心筋虚血再灌流傷害 / 心筋再生効果 / OXM-NP / 心保護効果 / プロスタサイクリンアゴニスト / ナノメディシン / 心筋虚血再灌流障害 / オキシム誘導体 / 心筋血管新生 / 心筋再生 / プロスタサイクリン作動薬 / DDS / 心筋虚血再灌流

Outline of Final Research Achievements

Intravenously injected OXM containing nanoparticles (OXM-NP), unlike an OXM-solution,selectively accumulated in the ischemia/reperfusion (I/R)-injured myocardium of rats and contributed to the prolonged retention of OXM in the targeted myocardial tissue. In the ischemic area, proangiogenic cytokines were up-regulated and inflammatory cytokines were down-regulated upon ONO-1301NP
administration. Consequently, ONO-1301NP-;injected rats exhibited a smaller infarct size, better-preserved capillary networks, and a better-preserved myocardial blood flow at 24 h after ischemia reperfusion injury, compared with those in vehicle-injected or ONO-1301 solution-;injected rats. OXM-NP attenuate the myocardial ischemia reperfusion injury via proangiogenic and anti-inflammatory effects of the drug.

Academic Significance and Societal Importance of the Research Achievements

本研究の結果、OXMを含有するNP（OXM-NP）をラット心筋虚血再灌流モデルに経静脈投与することにおいて、心筋虚血部位にOXM-NPが特異的に集積し、血管新生効果、抗炎症効果を介して心保護効果を発揮することが証明された。本研究結果を元とし、OXM-NPの最適な投与方法・投与量・対象疾患を同定し、前臨床試験、安全性試験および医師主導型治験の基礎データとする。本製剤は、様々な体内再生因子を持続的に放出させるという薬理作用から、心血管疾患だけでなく、各種難治性の呼吸器疾患、虚血性疾患、神経変性疾患、腎臓・肝臓疾患等々の疾患モデルに効果的である可能性を有しており、今後の発展性は高いものと考えられる。

Research Products

• [Journal Article] Prostacyclin Analog-Loaded Nanoparticles Attenuate Myocardial Ischemia/Reperfusion Injury in Rats (2019)
  • Author(s): Shin Yajima, Shigeru Miyagawa, Satsuki Fukushima, Yoshiki Sakai, Hiroko Iseoka, Akima Harada, Kayako Isohashi, Genki Horitsugi, Yuki Mori, Motoko Shiozaki, Hirotatsu Okawara, Ryoto Sakaniwa, Jun Hatazawa, Yoshichika Yoshioka, Yoshiki Sawa
  • Journal Title: Jounal of American College of Cardiology Basic to Translational Science Volume: 印刷中
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] A Prostacyclin Analogue-incorporated Nanoparticles Attenuates Ischemia Reperfusion Injury in Rat Heart (2017)
  • Author(s): 矢嶋真心
  • Organizer: American Heart Association Scientific Meeting 2017
  • Int'l Joint Research
• [Presentation] Injection of Nanoparticle-Prostacyclin Analogue Produces Cardioprotective Effect in a Rat I/R Model (2017)
  • Author(s): 矢嶋真心
  • Organizer: 第16回日本再生医療学会
• [Presentation] Intravenous Injection of Liposome-Based Nanoparticles Containing a Novel Prostacyclin Analogue Selectively Targets Ischemia-Reperfused Myocardium to Enhance Angiogenesis and Functional Recovery in Rat. (2016)
  • Author(s): 矢嶋真心
  • Organizer: American Heart Association Scientific Meeting 2016
  • Place of Presentation: New Orleans
  • Year and Date: 2016-11-11
  • Int'l Joint Research