Conquest of intractable lung disease due to lifestyle by pulmonary drug delivery system

• Project/Area Number: 17H02178
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied health science
• Research Institution: Hokkaido University of Science (2018-2020); Hokkaido Pharmaceutical University School of Pharmacy (2017)
• Principal Investigator: CHONO Sumio 北海道科学大学, 薬学部, 教授 (90347790)
• Co-Investigator(Kenkyū-buntansha): 戸上 紘平 北海道科学大学, 薬学部, 准教授 (20582357) ; 板垣 史郎 札幌医科大学, その他部局等, 准教授 (00360925)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000); Fiscal Year 2020: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
• Keywords: 難治性肺疾患 / 肺投与型DDS / 検査・治療 / 薬物服用習慣 / 肺線維症 / ニンテダニブ / 可溶化 / DDS / リポソーム / 生活習慣病 / 肺投与 / 肺内滞留性

Outline of Final Research Achievements

For conquest of intractable lung disease due to lifestyle, pulmonary drug delivery system (DDS) for the lesion detection and treatment of these diseases was developed. In brief, the lipid nano formulations for pulmonary administration were prepared for inspection and treatment of lung cancer and pulmonary fibrosis in the near future, and their intrapulmonary behaviors, efficacy and safety were demonstrated.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、肺がんや肺線維症などライフスタイルに発症起因する難治性肺疾患を検査と治療の両側面からマルチに征圧する学術的・臨床的基盤を提案するものである。また、本研究の成果は、これらの疾患を早期発見・早期治療に導くものであり、医学的に極めて重要な知見をもたらしたことは勿論、臨床実用化に至った暁には、医療費高騰の抑制など社会的にも非常に大きな意義がある。

Research Products

• [Journal Article] Assessment of transporter-mediated efflux of nintedanib using in vitro cell line models of idiopathic pulmonary fibrosis (2020)
  • Author(s): Togami K, Yamaguchi K, Tada H, Chono S
  • Journal Title: Die Pharmazie Volume: 75 Pages: 371-374
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Prolonged distribution of aerosolized PEGylated liposomes in the lungs of mice with bleomycininduced pulmonary fibrosis (2020)
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Multiscale live imaging using Forster Resonance Energy Transfer (FRET) for evaluating the biological behavior of nanoparticles as drug carriers (2020)
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Evaluation of tissue-clearing techniques for intraorgan imaging of distribution of polymeric nanoparticles as drug carriers (2020)
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Three-dimensional imaging of pulmonary fibrotic foci at the alveolar scale using tissueclearing treatment with staining techniques of extracellular matrix (2020)
  • 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
  • Peer Reviewed / Open Access / 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 scale (2019)
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Conditional examinations for pulverization of lansoprazole orally disintegrating tablets (2019)
  • Author(s): Chono S, Nakamura K, Matsui M
  • Journal Title: J. Generic Med. Volume: 15(3) Issue: 3 Pages: 99-103
  • DOI: 10.1177/1741134319827064
  • Peer Reviewed / 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 cancer (2019)
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Facile and sensitive HPLC-UV method for determination of nintedanib in rat plasma (2018)
  • Author(s): Togami K, Fukuda K, Yamaguchi K, Chono S, Tada H
  • Journal Title: Int. J. Pharm. Pharm. Sci. Volume: 10 Issue: 6 Pages: 133-137
  • DOI: 10.22159/ijpps.2018v10i6.25504
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Tissue-Clearing Techniques Enable Three-Dimensional Visualization of Aerosolized Model Compound and Lung Structure at the Alveolar Scale (2018)
  • Author(s): Kohei Togami, Anri Kitayama, Takayuki Daisho, Rui Wang, Hitoshi Tada, Sumio Chono
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 41 Issue: 1 Pages: 24-28
  • DOI: 10.1248/bpb.b17-00348
  • NAID: 130006301224
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evaluation of permeability alteration and epithelial-mesenchymal transition induced by transforming growth factor-<beta>1 in A549, NCI-H441, and Calu-3 cells: development of an in vitro model of respiratory epithelial cells in idiopathic pulmonary fibrosis (2017)
  • Author(s): Kohei Togami, Kotaro Yamaguchi, Sumio Chono, Hitoshi Tada
  • Journal Title: Journal of Pharmacological and Toxicological Methods Volume: 86 Pages: 19-27
  • DOI: 10.1016/j.vascn.2017.02.023
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Aerosolized liposomes with dipalmitoyl phosphatidylcholine enhance pulmonary absorption of encapsulated insulin compared with co-administered insulin (2017)
  • Author(s): Chono S, Togami K, Itagaki S
  • Journal Title: Drug Dev. Ind. Pharm. Volume: 43 Issue: 11 Pages: 1892-1898
  • DOI: 10.1080/03639045.2017.1353521
  • Peer Reviewed / Int'l Joint Research
• [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
• [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
• [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（富山）
• [Presentation] ドラッグキャリアの体内動態を可視化するreal-time FRET imaging (2019)
  • 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（横浜）
• [Presentation] Multiscale live-imaging using Forster resonance energy transfer to evaluate the distribution of nanoparticles for drug delivery (2019)
  • Author(s): Ishizawa K, Togami K, Tada H, Chono S
  • Organizer: Controlled Release Society 2019 Annual Meeting & Exposition, Valencia, Spain（
  • Int'l Joint Research
• [Presentation] Efficient delivery to fibrotic regions of liposomes modified with fibroblast- and collagen-targeting peptides for the treatment of idiopathic pulmonary fibrosis (2019)
  • Author(s): Togami K, Hirotsugu Ishii, Ryota Abe, Tada H, Chono S
  • Organizer: Controlled Release Society 2019 Annual Meeting & Exposition, Valencia, Spain
  • Int'l Joint Research
• [Presentation] ドラッグデリバリーシステム（DDS）が拓く次世代の創薬・創剤 (2019)
  • Author(s): 丁野純男
  • Organizer: 第33回北海道薬物作用談話会
  • Invited
• [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 (2019)
  • 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（京都）
• [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（千葉）
• [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: 日本薬学会第145回支部例会（札幌）
• [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: 日本薬学会第145回支部例会（札幌）
• [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: 日本薬学会第145回支部例会（札幌）
• [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（静岡）
• [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 imaging (2018)
  • 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（長崎）
• [Presentation] Multi-scale imaging using Forster resonance energy transfer for evaluating drug carrier distribution (2018)
  • Author(s): Ishizawa K, Togami K, Tada H, Chono S
  • Organizer: 2018 AAPS PharmSci 360, Washington DC, USA.
  • Int'l Joint Research
• [Presentation] ドラッグデリバリーシステムに用いるナノ粒子の体内分布特性評価を目的としたマルチスケールイメージング手法の確立 (2018)
  • Author(s): 石澤清心, 戸上紘平, 多田均, 丁野純男
  • Organizer: 日本薬学会第138年会
• [Presentation] 肺線維症モデルマウスにおける薬物封入リポソーム肺投与後の肺内滞留性に関する検討 (2018)
  • Author(s): 金澤楓, 戸上紘平, 兼平幸宗, 多田均, 丁野 純男
  • Organizer: 日本薬学会第138年会
• [Presentation] 肺線維症発症時における肺胞閉塞に伴う肺投与型薬物の肺内分布の変化 (2017)
  • Author(s): 戸上紘平, 弓田有輝, 大聖貴之, 王鋭, 多田均, 丁野純男
  • Organizer: 日本薬剤学会第32年会
• [Presentation] DPPCリポソームはインスリン未封入体よりも封入体の経肺吸収を優位に促進する (2017)
  • Author(s): 戸上紘平, 丁野純男
  • Organizer: 第33年会日本DDS学会
• [Presentation] Influence of extracellular matrix in fibrotic lesions on the distribution of aerosolized drugs (2017)
  • Author(s): Togami K, Yumita Y, Daisho T, Kitayama A, Tada H, Chono S
  • Organizer: Drug Discovery and Therapy World Congress 2017
  • Int'l Joint Research
• [Book] 次世代吸入製剤とデバイスの開発 (2018)
  • Author(s): 丁野純男
  • Total Pages: 252
  • Publisher: シーエムシー出版
  • ISBN: 9784781313535