| Project/Area Number |
18K06611
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
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| Research Institution | Aichi Gakuin University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | 潰瘍性大腸炎 / 高分子ナノ粒子 / 高分子ミセル / デコイ核酸 / エマルション溶媒拡散法 / ポリ乳酸グリコール酸 / ナノ粒子 / 粘膜付着性 / ドラッグデリバリーシステム / 核酸医薬 / 経口投与製剤 |
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| Outline of Final Research Achievements |
The aim of this study was to develop a new polymeric nanoparticle/polymeric nanomicelle DDS formulation for orally administered nucleic acid drug delivery that utilizes the tissue penetration ability of polymeric nanoparticles and polymeric micelles to orally administer nanoparticles/nanomicelles encapsulating oligodecoy nucleic acids that suppress NF-κB, which is related to inflammatory cytokine production, and that can achieve remission and complete cure of ulcerative colitis, which has been considered difficult to treat. Nanopolymer micelles with fine particle size show higher tissue migration than polymeric nanoparticles, and this rate was further improved by modifying them with chitosan. The drug encapsulation rate in the nanoparticles was improved by complexing the decoy nucleic acid with cationic lipids. Cytokine production was suppressed by administering nanoparticles encapsulating decoy nucleic acids.
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| Academic Significance and Societal Importance of the Research Achievements |
高分子ミセルや高分子ナノ粒子へ、デコイ核酸を効率よく封入する調製法を確立した。この調製法はsiRNAやプラスミドDNAなどの核酸医薬に広く適用可能であり、様々な疾患の治療に応用できる。また、より微細な粒子である程、消化管組織への分布量が多くなることを示し、薬物送達の効率化ならびに薬物の作用時間の持続化も期待できることを明らかにした。病気に苦しむ多くの患者に有益な成果をもたらす有意義な結果を示すことができた。
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