2020 Fiscal Year Final Research Report
Development of an oral nucleic acid delivery system accelerating the paradigm shift to nucleic acid pharmaceutical products
| Project/Area Number |
18H03541
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 90120:Biomaterials-related
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| Research Institution | Osaka Ohtani University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
渡辺 知恵 城西大学, 薬学部, 准教授 (30737747)
松本 昭博 大阪大谷大学, 薬学部, 准教授 (80824911)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | バイオ医薬品 / 経口製剤 / 薬物送達システム / 多孔性ヤヌス微粒子 / 核酸医薬 / 脂質ナノ粒子 / 粘膜付着性 / 大腸デリバリー |
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| Outline of Final Research Achievements |
To reduce losses due to decomposition, adsorption, dilution, etc. of biopharmaceuticals such as nucleic acid drugs in the digestive tract and to achieve absorption improvement by producing high concentration in the limited local absorption area of intestinal mucosa, porous Janus particles with mucosal adhesion function only in the porous hemisphere were newly designed and prepared. When lipid nanoparticles containing alpha-tocopherol-modified siRNA were impregnated in the porous preparation, filled with conventional enteric capsules and administered orally to rats, the siRNA molecules were markedly detected in the target hepatocytes. Porous Janus particles have been indicated to be useful as a platform for oral drugization to facilitate a paradigm shift to biopharmaceuticals because they are versatile, high drug loading, easy to multifunctional, and avoid physicochemical stress in the fabrication process such as emulsification.
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| Free Research Field |
ドラッグデリバリーシステム
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| Academic Significance and Societal Importance of the Research Achievements |
核酸医薬等バイオ医薬は難治性疾患や慢性疾患の原因・根本治療につながる次世代医薬として期待されるが、そのパラダイムシフトのボトルネックは、高額な医薬品の経口薬化である。本研究は、阻害要因を、高価な医薬の製剤化・吸収過程における損失、粘膜不透過性、製剤化技術情報の不足と捉え、これらの課題を解決し得る方法を提案し、開発の可能性を示した。一方、高分子を含めた相分離によるヤヌス型微粒子の製造や、ぬれ性による薬物含量や放出の制御など、製剤化に関する理論的考察は、この分野の学術情報としても価値がある。又、ヤヌスナノ微粒子の粘膜上の分布では、予想に反する知見も得られており、吸収改善機構は学術上の課題でもある。
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