• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Efficient drug delivery to lung tumor and pulmonary fibrotic foci by intrapulmonary administration of the lipid nanoparticles

Research Project

Project/Area Number 18K06603
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
Research InstitutionHokkaido University of Science

Principal Investigator

Togami Kohei  北海道科学大学, 薬学部, 准教授 (20582357)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords肺がん / 肺線維症 / 吸入型製剤 / ドラッグデリバリーシステム / リポソーム / siRNA / 蛍光イメージング / 分子標的薬 / 脂質ナノ粒子 / コラーゲン / ナノ粒子 / 肺投与 / in vivo imaging / 肺線維芽細胞 / 細胞外マトリックス / DDS
Outline of Final Research Achievements

This study evaluated the delivery efficiency of the intrapulmonary administration of antitumor small interfering ribonucleic acid (siRNA) and antifibrotic agents-containing nanoparticles to mice with metastatic lung tumor and bleomycin-induced pulmonary fibrosis. Fluorescence-labeled, siRNA-containing nanoparticles and liposomes were administered using Liquid MicroSprayer. Fluorescent signals in the whole lung and in the tumor region following the intrapulmonary administration of the nanoparticles and liposomes were strong and sustained. These systems may be useful for the sustained distribution of anti-tumor siRNAs and anti-fibrotic agents in tumor or fibrotic lungs and the optimization of therapy of respiratory diseases.

Academic Significance and Societal Importance of the Research Achievements

難治性呼吸器疾患である肺がん及び肺線維症の治療を指向したDDSを構築することで、現在使用されている治療薬をより安全に、より有効に用いた治療可能性を見出すことができる。また、これまでin vivoで十分な効果が得られなかった治療薬候補化合物の再開発が可能となり、QOLの低い難治性呼吸器疾患の治療ツールとして大変意義深いものである。さらに、呼吸器疾患以外においても細胞外マトリックスなどの線維組織の存在により、薬物の到達不足が問題になる例が散見されている。したがって、線維組織による薬物送達障壁を克服する本研究は、呼吸器疾患のみならず幅広い疾患におけるDDS構築に新概念を提唱することを可能とする。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (25 results)

All 2020 2019 2018

All Journal Article (10 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 10 results,  Open Access: 4 results) Presentation (15 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] Intrapulmonary Pharmacokinetics and Drug Distribution Characteristics for the Treatment of Respiratory Diseases2020

    • Author(s)
      Togami Kohei
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 140 Issue: 3 Pages: 345-354

    • DOI

      10.1248/yakushi.19-00155

    • NAID

      130007803976

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2020-03-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multiscale live imaging using Forster Resonance Energy Transfer (FRET) for evaluating the biological behavior of nanoparticles as drug carriers2020

    • Author(s)
      Ishizawa K, Togami K, Tada H, Chono S
    • Journal Title

      J.Pharm.Sci.

      Volume: 109 Issue: 12 Pages: 3608-3616

    • DOI

      10.1016/j.xphs.2020.08.028

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Prolonged distribution of aerosolized PEGylated liposomes in the lungs of mice with bleomycininduced pulmonary fibrosis2020

    • Author(s)
      Togami K, Maruta Y, Nanbu M, Tada H, Chono S
    • Journal Title

      Drug Dev. Ind. Pharm.

      Volume: 46 Issue: 11 Pages: 1873-1880

    • DOI

      10.1080/03639045.2020.1825473

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Evaluation of tissue-clearing techniques for intraorgan imaging of distribution of polymeric nanoparticles as drug carriers2020

    • Author(s)
      Ishizawa K, Togami K, Tada H, Chono S
    • Journal Title

      Drug Dev. Ind. Pharm.

      Volume: 46 Issue: 12 Pages: 2061-2069

    • DOI

      10.1080/03639045.2020.1843476

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Assessment of transporter-mediated efflux of nintedanib using in vitro cell line models of idiopathic pulmonary fibrosis2020

    • Author(s)
      Togami Kohei、Yamaguchi Kotaro、Tada Hitoshi、Chono Sumio
    • Journal Title

      Pharmazie

      Volume: 75 Pages: 371-374

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aerosolized Liposomal Formulation Prevents Enhanced Drug Transfer from Fibrotic Lungs to the Systemic Circulation2020

    • Author(s)
      Togami Kohei、Kurasho Kaede、Kanehira Yukimune、Tada Hitoshi、Chono Sumio
    • Journal Title

      Current Drug Delivery

      Volume: 18 Issue: 7 Pages: 923-930

    • DOI

      10.2174/1567201818666201229154143

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Three-dimensional imaging of pulmonary fibrotic foci at the alveolar scale using tissueclearing treatment with staining techniques of extracellular matrix2020

    • Author(s)
      Togami K, Ozaki H, Yumita Y, Kitayama A, Tada H, Chono S
    • Journal Title

      Int. J. Biomed. Imaging

      Volume: 2020 Pages: 8815231-8815231

    • DOI

      10.1155/2020/8815231

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intratumoral delivery and therapeutic efficacy of nanoparticle-encapsulated anti-tumor siRNA following intrapulmonary administration for potential treatment of lung cancer2019

    • Author(s)
      Kanehira Yukimune、Togami Kohei、Ishizawa Kiyomi、Sato Shingo、Tada Hitoshi、Chono Sumio
    • Journal Title

      Pharmaceutical Development and Technology

      Volume: 24 Issue: 9 Pages: 1095-1103

    • DOI

      10.1080/10837450.2019.1633345

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Evaluation of various tissue-clearing techniques for the three-dimensional visualization of liposome distribution in mouse lungs at the alveolar scale2019

    • Author(s)
      Kohei Togami, Takayuki Daisho, Yuki Yumita, Anri Kitayama, Hitoshi Tada, Sumio Chono
    • Journal Title

      International Journal of Pharmaceutics

      Volume: 562 Pages: 218-227

    • DOI

      10.1016/j.ijpharm.2019.03.032

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Facile and sensitive HPLC-UV method for determination of nintedanib in rat plasma2018

    • Author(s)
      Kohei Togami, Kenta Fukuda, Kotaro Yamaguchi, Hitoshi Tada, Sumio Chono
    • Journal Title

      International Journal of Pharmacy and Pharmaceutical Science

      Volume: 10 Pages: 133-137

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] シクロデキストリン複合体化による抗線維化薬ニンテダニブの肺内動態および肺線維症治療効果の改善2020

    • Author(s)
      戸上紘平, 岩田健嗣, 小笠原安理沙, 入江沙世, 山口広太郞, 多田均, 丁野純男
    • Organizer
      日本薬剤学会第35年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 抗線維化薬ニンテダニブ-シクロデキストリン複合体の肺投与による肺内動態および肺線維症治療効果の改善2020

    • Author(s)
      戸上紘平,小笠原安理沙,入江沙世,岩田健嗣,山口広太郎,多田均,丁野純男
    • Organizer
      第36回日本DDS学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ヒドロキシプロピル-γ-シクロデキストリンを用いた抗線維化薬ニンテダニブ肺投与の有用性2020

    • Author(s)
      戸上 紘平、小笠原 安理沙、入江 沙世、岩田 健嗣、山口 広太郎、多田 均、丁野 純男
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Real-time FRET imagingによるドラッグキャリアの体内動態の可視化2019

    • Author(s)
      石澤清心, 戸上紘平, 多田均, 丁野純男
    • Organizer
      日本薬剤学会第34年会
    • Related Report
      2019 Research-status Report
  • [Presentation] ドラッグキャリアの体内動態を可視化するreal-time FRET imaging2019

    • Author(s)
      石澤清心, 戸上紘平, 多田均, 丁野純男
    • Organizer
      第35回日本DDS学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Efficient delivery to fibrotic regions of liposomes modified with fibroblasts and collagen targeting for treatment in idiopathic pulmonary fibrosis2019

    • Author(s)
      Kohei Togami, Hirotsugu Ishii, Ryota Abe, Hitoshi Tada, Sumio Chono
    • Organizer
      CRS 2019 Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Multiscale live-imaging using F?rster resonance energy transfer to evaluate the distribution of nanoparticles for drug delivery2019

    • Author(s)
      Kiyomi Ishizawa, Kohei Togami, Hitoshi Tada, Sumio Chono
    • Organizer
      CRS 2019 Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 肺線維症治療を指向したリポソームの肺線維芽細胞への集積性およびcollagen Iへの付着性に関する検討2019

    • Author(s)
      戸上紘平、石井大嗣、阿部亮太、多田均、丁野純男
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Multi-scale imaging using Forster resonance energy transfer for evaluating drug carrier distribution2018

    • Author(s)
      Kiyomi Ishizawa, Kohei Togami, Hitoshi Tada, Sumio Chono
    • Organizer
      AAPS 2018 PHARMSCI 360
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] ドラッグキャリアに用いるナノ粒子と内封薬物の体内分布評価のためのFRET現象を応用したmulti-scale imaging2018

    • Author(s)
      石澤清心、戸上紘平、多田均、丁野純男
    • Organizer
      第34回日本DDS学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] FRET現象を応用したmulti-scale imagingによるドラッグキャリアと内封薬物の体内分布評価法の確立2018

    • Author(s)
      石澤清心、戸上紘平、多田均、丁野純男
    • Organizer
      日本薬剤学会第33年会
    • Related Report
      2018 Research-status Report
  • [Presentation] FRET現象を応用したmulti-scale imagingによるDDSの機能評価法の確立2018

    • Author(s)
      石澤清心、戸上紘平、多田均、丁野純男
    • Organizer
      日本薬学会北海道支部第145例会
    • Related Report
      2018 Research-status Report
  • [Presentation] 肺線維症発症時における肺投与型リポソームの肺内滞留性に関する検討2018

    • Author(s)
      藏所楓、兼平幸宗、多田均、丁野純男、戸上紘平
    • Organizer
      日本薬学会北海道支部第145例会
    • Related Report
      2018 Research-status Report
  • [Presentation] 肺線維症の病巣細胞によるニンテダニブの取り込みに及ぼす排出トランスポーターの影響2018

    • Author(s)
      山口広太郎、丁野純男、多田均、戸上紘平
    • Organizer
      日本薬学会北海道支部第145例会
    • Related Report
      2018 Research-status Report
  • [Presentation] 呼吸器疾患治療のための薬物の肺内動態および肺組織分布特性の解明2018

    • Author(s)
      戸上紘平
    • Organizer
      日本薬学会北海道支部第145例会奨励賞受賞講演
    • Related Report
      2018 Research-status Report
    • Invited

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi