| Project/Area Number |
26860029
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Physical pharmacy
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| Research Institution | Meijo University |
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Principal Investigator |
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| Research Collaborator |
OKAMOTO Hirokazu 名城大学, 薬学部, 教授 (00308941)
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 自己組織化ナノ粒子 / 吸入粉末剤 / 粒子設計 / sIRNA / 遺伝子治療 / 核酸デリバリー / 噴霧急速凍結乾燥法 / 中空多孔性微粒子 / siRNA / 多孔性微粒子 |
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| Outline of Final Research Achievements |
The aim of the present study was to develop innovative dry siRNA powders for inhalation that show pulmonary gene silencing action through spontaneous constitution of siRNA/lipid nanoparticles in the lungs, which was produced by the novel combination of two particle design techniques: spray freeze drying for highly porous microparticles with high aerosol performance and self-assembly of lipid nanoparticles in water. The component optimization (i.e. cationic lipids, polyethylene glycol derivatives, and excipients) achieved successful production of dry siRNA powders with high aerosol performance that allow self-assembly of siRNA/lipid nanoparticles with high gene silencing activity and low cytotoxicity in water. The dry siRNA powders were demonstrated to have prolonged retention ability and improved biostability of siRNA in the lungs through spontaneous nanoparticle constitution after pulmonary delivery, subsequently leading to strong and specific gene silencing action in the lungs.
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