2022 Fiscal Year Final Research Report
Construction of optimum composition of the posterior segment-directed nanoparticle eyedrop via particle characterization and intraocular migration
| Project/Area Number |
20K12652
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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 90120:Biomaterials-related
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | siRNA delivery / 網膜 / ナノ粒子 / リポソーム / 点眼 |
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| Outline of Final Research Achievements |
The aim was to optimize the preparation process and formulation of nanoparticle eye drops that enable noninvasive treatment and prevention of retinal diseases based on evaluation of particle structural characteristics (surface potential, particle structure, composition, etc.) and intraocular migration after instillation in rats. Nucleic acid (siRNA)-loaded nanoparticles modified with hyaluronic acid (HA), which targets CD44 receptors highly expressed in the retina, or with multifunctional peptide were prepared. An appropriate preparation process of HA-modified nanoparticles exhibiting efficient intracellular and intraocular behavior as eye drops was established. By designing a particle composition which is predicted to retain siRNA on both the particle surface and peptide moiety, the nanoparticles showed that the efficient intraocular migration to the retina after instillation to rat and significant silencing effect.
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| Free Research Field |
製剤設計学、薬物送達学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究において、完治に至る薬物療法がない網膜疾患に対し、薬物送達の妨げとなる血液網膜関門等の高度なバリア機能を回避し、網膜まで到達し得るナノ粒子担体を再現性良く提供する核酸搭載ナノ粒子点眼剤の調製プロセスと処方を、粒子構造・物性評価、眼内組織移行性と粒子素材との関連性に基づき設定した。本研究での知見は、従来の硝子体内注射による薬物療法に比べ、患者による自己管理・自己投与が可能でQOL及びアドヒアランスを向上する低侵襲的点眼剤創出のための基盤となることが期待される。
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