Development of nucleic acid delivery nano-DDS based on nose-to-brain route and its application to glia targeted therapy

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H04537
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 90120:Biomaterials-related
• Research Institution: University of Shizuoka
• Principal Investigator: Takanori Kanazawa 静岡県立大学, 薬学部, 准教授 (60434015)
• Co-Investigator(Kenkyū-buntansha): 田中 浩揮 千葉大学, 大学院薬学研究院, 助教 (60801743) ; 小菅 康弘 日本大学, 薬学部, 教授 (70383726)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Nose-to-Brain / 核酸DDS / ナノ粒子 / グリア標的治療

Outline of Final Research Achievements

In this study, to establish nose-to-brain nanoDDS technology for nucleic acid drugs targeting the forebrain (cerebral cortex and hippocampus), liposomes with various properties were analyzed for their nose-to-brain transfer kinetics, and it was found that PEG-modified and positively charged liposomes are suitable nanocarrier properties for delivery selectively to the forebrain. In addition, nanoparticles composed of PEG-block polymers/functional peptides with a positive surface charge and a particle size of less than 50 nm showed remarkably strong target gene knockdown in the cerebral cortex and hippocampus by nucleic acid drugs, demonstrating a superior therapeutic effects on mice with cerebral ischemia/reperfusion injury.

Free Research Field

薬物送達学

Academic Significance and Societal Importance of the Research Achievements

本研究で得られた成果は、中枢神経系への核酸DDS技術の開発に関する重要な情報を提供するものと期待される。また、本研究を通じて確立した再現性の高い多成分系共集合化ナノ粒子の調製手法ならびにナノ粒子を用いた大脳皮質や海馬のミクログリアを標的とするNose-to-BrainナノDDS技術による核酸治療システムは、認知症をはじめとする様々な中枢神経系疾患患に対する非侵襲的薬物治療開発における重要な基盤技術となり得ると考える。