Rho-kinase inhibitor targeting the liver prevents liver fibrosis without major systemic adversity in rats

Research Project

Project/Area Number	26861078
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Digestive surgery
Research Institution	Hiroshima University
Principal Investigator	Shintaro Kuroda 広島大学, 大学病院, 医科診療医 (30457246)
Project Period (FY)	2014-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000) Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000) Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords	肝線維化 / 星細胞 / リポソーム / DDS / Rhoキナーゼ阻害剤 / 肝星細胞 / Drug Delivery System
Outline of Final Research Achievements	Rho-kinase (ROCK) inhibitors improve liver blood flow after ischemia/reperfusion (IR) injury or improve liver fibrosis, by preventing the activation of hepatic stellate cell (HSC). However, the systemic administration of ROCK inhibitors causes severe hypotension; therefore, liver-specific ROCK inhibition is required. Here, we tested vitamin A coupled liposomes carrying the ROCK inhibitor for targeted HSCs in rat IR model and liver fibrosis model. Liposomal ROCK inhibitor was 100-fold more effective in inhibiting HSC activation than free ROCK inhibitor without major systemic adversity in rats.

Report

(3 results)