Development of a novel DDS targeting ischemic stroke region by using leukocyte-like function and control of brain microenvironment via faint electricity

2018 Fiscal Year Final Research Report

• Project/Area Number: 17H06906
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Physical pharmacy
• Research Institution: The University of Tokushima
• Principal Investigator: FUKUTA Tatsuya 徳島大学, 大学院医歯薬学研究部(薬学域), 助教 (90805160)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Keywords: 脳梗塞 / 血液脳関門 / リポソーム / 白血球 / 膜タンパク質 / 脂質膜間移行 / 炎症血管内皮 / 微弱電流

Outline of Final Research Achievements

We previously demonstrated that drug delivery with nano-sized liposomes is available for the treatment of ischemic stroke via passage through the disintegrated blood-brain barrier (BBB) after a stroke. However, liposomal entry into the brain parenchyma was limited at an early phase following ischemia/reperfusion. As leukocytes can pass through the BBB regardless of such conditions via utilizing the functions of their membrane proteins, we hypothesized that incorporation of leukocyte membrane proteins onto liposomal membranes may impart leukocyte-mimicking functions to liposomes. In this research, we developed leukocyte-mimetic liposomes (LM-Lipo) by leukocyte membrane protein transfer and evaluated their function in vitro. The results suggested that transfer of leukocyte membrane proteins onto liposomes could allow for association of the liposomes with inflamed endothelial cells, and subsequent passage through the inflamed endothelial cell layer via change of intercellular junctions.

Free Research Field

薬物送達学

Academic Significance and Societal Importance of the Research Achievements

学術的な意義として、本研究成果がさらに発展し、白血球が有する生体機能を模倣したリポソームを構築することで、ナノ粒子を用いた脳梗塞治療が抱える課題を解決し、脳への薬物送達の最大の障壁である血液脳関門を突破可能な新規薬物送達システム（DDS）の開発に繋がり得る点が挙げられる。社会的意義として、脳梗塞に対する新たな治療薬の開発に貢献でき、患者QOLの向上と、超高齢社会で問題とされる要介護人口の減少と医療経済の改善に繋がることが期待される。