New development of pulmonary fibrosis therapy based on pulmonary drug delivery technology with fibrinolysis functions

• Project/Area Number: 25870654
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Physical pharmacy; Pharmacology in pharmacy
• Research Institution: Hokkaido Pharmaceutical University School of Pharmacy
• Principal Investigator: Chono Sumio 北海道薬科大学, 薬学部, 教授 (90347790)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 肺線維症 / 肺線維芽細胞 / ピルフェニドン / bFGF修飾リポソーム / 経気道投与型ドラッグデリバリーシステム / コラーゲン産生 / 経気道局所治療 / リポソーム

Outline of Final Research Achievements

Liposomal pirfenidone as a anti-fibrotic drug formulation was designed and prepared, and its efficacy as a pulmonary drug delivery system for treatment of pulmonary fibrosis was evaluated. Liposomal pirfenidone was efficiently delivered to fibroblasts and it inhibited collagen production in fibroblasts. This study suggests that aerosol-based liposomal pirfenidone is a new therapeutic strategy.

Research Products

• [Journal Article] Alteration in intrapulmonary pharmacokinetics of aerosolized model compounds due to disruption of the alveolar epithelial barriers following bleomycin-induced pulmonary fibrosis in rats. (2016)
  • Author(s): Kohei Togami, Sumio Chino, Hitoshi Tada
  • Journal Title: Journal of Pharmaceutical Sciences Volume: 105 Issue: 3 Pages: 1327-1334
  • DOI: 10.1016/j.xphs.2015.12.010
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Tumor distribution and anti-tumor effect of doxorubicin following intrapulmonary administration to mice with metastatic lung tumor. (2016)
  • Author(s): Yukimune Kanehira, Kohei Togami, Hitoshi Tada, Sumio Chino
  • Journal Title: Journal of Drug Delivery Science and Technology Volume: 33 Pages: 143-146
  • DOI: 10.1016/j.jddst.2016.04.001
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Efficient Delivery to Human Lung Fibroblasts (WI-38) of Pirfenidone Incorporated into Liposomes Modified with Truncated Basic Fibroblast Growth Factor and Its Inhibitory Effect on Collagen Synthesis in Idiopathic Pulmonary Fibrosis (2015)
  • Author(s): Kohei Togami, Aki Miyao, Kei Miyakoshi, Yukimune Kanehira, Hitoshi Tada, Sumio Chono
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 38 Issue: 2 Pages: 270-276
  • DOI: 10.1248/bpb.b14-00659
  • NAID: 130004872262
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 肺線維症発症時における肺胞上皮細胞のタイトジャンクション障害に基づく肺投与型薬物の肺内動態変化 (2016)
  • Author(s): 戸上紘平, 丁野純男, 多田均
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-28
• [Presentation] Altered intrapulmonary pharmacokinetics of aerosolized drugs due to the disruption of the alveolar epithelial barrier in animals with bleomycin-induced pulmonary fibrosis (2015)
  • Author(s): Togami K, Tada H, Chono S
  • Organizer: 2015 AAPS Annual Meeting and Exposition
  • Place of Presentation: Orlando, FL, USA
  • Year and Date: 2015-10-25
  • Int'l Joint Research
• [Presentation] 肺線維症モデル動物における肺投与した薬物の肺内動態特性 (2015)
  • Author(s): 戸上紘平，多田均，丁野純男
  • Organizer: 日本薬剤学会第30年会
  • Place of Presentation: 長崎
  • Year and Date: 2015-05-21
• [Presentation] 転移性肺がんモデルマウスにおける肺投与薬物の肺腫瘍組織への分布特性 (2015)
  • Author(s): 兼平幸宗, 戸上紘平, 多田均, 丁野純男
  • Organizer: 第62回北海道薬学大会
  • Place of Presentation: 札幌
  • Year and Date: 2015-05-17
• [Presentation] 肺線維症モデル動物における肺投与型薬物の肺内滞留性及び肺胞深部への到達性に関する検討 (2015)
  • Author(s): 戸上紘平, 丁野純男, 多田均
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] Intrapulmonary pharmacokinetics of aerosolized drugs in animals with bleomycin-induced pulmonary fibrosis (2014)
  • Author(s): Togami K, Tada H, Chono S
  • Organizer: 19th North American ISSX / 29th JSSX Meeting
  • Place of Presentation: San Francisco
  • Year and Date: 2014-10-19 – 2014-10-23
• [Presentation] 肺線維症の治療を指向したbasic fibroblast growth factor（bFGF）修飾リポソームの肺線維芽細胞への標的指向化 (2014)
  • Author(s): 戸上紘平, 宮尾亜希, 宮腰恵生, 多田均, 丁野純男
  • Organizer: 第30回日本DDS学会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-30 – 2014-07-31
• [Presentation] 肺線維症の治療を指向した basic fibroblast growth factor (bFGF) 修飾リポソームの肺線維芽細胞への標的指向化に関する研究
  • Author(s): 宮尾亜希,宮腰恵生,戸上紘平,多田 均,丁野純男
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
• [Presentation] 肺線維症モデル動物における肺投与後の肺内動態に関する検討
  • Author(s): 戸上紘平,多田 均,丁野純男
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
• [Presentation] 肺線維症モデル動物における肺投与型製剤の肺内動態に関する検討
  • Author(s): 戸上紘平,多田均,丁野純男
  • Organizer: 日本薬剤学会第29年会
  • Place of Presentation: 大宮