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Development of an oral nucleic acid delivery system accelerating the paradigm shift to nucleic acid pharmaceutical products

Research Project

Project/Area Number 18H03541
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 90120:Biomaterials-related
Research InstitutionOsaka Ohtani University

Principal Investigator

Murakami Masahiro  大阪大谷大学, 薬学部, 教授 (50174280)

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)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
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 / 多孔性ヤヌス粒子 / siRNA / ドラッグデリバリーシステム / DDS / 経口デリバリー / ヤヌス微粒子 / ポーラスヤヌス微粒子 / 核酸分子 / インスリン / 経口送達システム / 核酸医薬品 / 多孔性マイクロスフェア / 腸管粘膜付着性 / Caco-2 / 経口核酸送達システム
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.

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。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (12 results)

All 2021 2020 2019

All Journal Article (3 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (7 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Dry fabrication of poly(<i>dl</i>-lactide-co-glycolide) microspheres incorporating a medium molecular drug by a ball mill method2021

    • Author(s)
      Matsumoto Akihiro、Murakami Masahiro
    • Journal Title

      Drug Discoveries & Therapeutics

      Volume: 15 Issue: 1 Pages: 20-27

    • DOI

      10.5582/ddt.2021.01004

    • NAID

      130007996713

    • ISSN
      1881-7831, 1881-784X
    • Year and Date
      2021-02-28
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 核酸医薬品へのパラダイムシフトを加速する 経口核酸送達システムの開発戦略2020

    • Author(s)
      村上 正裕、渡辺 知恵、松本 昭博
    • Journal Title

      月刊「細胞」

      Volume: 52 Pages: 53-59

    • NAID

      40022320372

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Janus microspheres for enhanced enteral drug delivery: Preparation and orientated attachment to a Caco-2 monolayer2019

    • Author(s)
      Akihiro Matsumoto, Chie Watanabe, Masahiro Murakami
    • Journal Title

      Drug Discoveries & Therapeutics

      Volume: 13 Issue: 6 Pages: 343-353

    • DOI

      10.5582/ddt.2019.01090

    • NAID

      130007788595

    • ISSN
      1881-7831, 1881-784X
    • Year and Date
      2019-12-31
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Improved hepatic delivery of siRNA by condensed drug loading in a dimpled suppository2021

    • Author(s)
      Akihiro Matsumoto, Chie Watanabe, Masahiro Murakam
    • Organizer
      Pharma R&D 2021
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 乳酸・グリコール酸共重合体マイクロスフェアの溶媒フリー製法:表面解析及び熱力学的特性の評価2021

    • Author(s)
      松添誠、松本昭博、村上正裕
    • Organizer
      日本薬学会 第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ディンプル型坐剤によるLabrasolの吸収促進作用の増強効果2020

    • Author(s)
      村尾聡、谷川友亮、松本昭博、村上正裕
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 乳酸・グリコール酸コポリマー‐マイクロスフェアの溶媒フリー製法の開発:製造条件の検討及び液中乾燥法との比較2020

    • Author(s)
      西口未紗、松本昭博、村上正裕
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Use of porous microsphere-containing suppository in the hepatocyte-specific enteral delivery system for the delivery of siRNA.2019

    • Author(s)
      Akihiro Matsumoto, Chie Watanabe, Masahiro Murakami
    • Organizer
      46th Controlled Release Society Annual Meeting & Exposition (Valencia, Spain)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Systemic liver-targeting delivery of a novel DNA/RNA heteroduplex oligonucleotide via an enteral route2019

    • Author(s)
      Chie Watanabe, Masahiro Murakami
    • Organizer
      3rd Edition of Global Conference on Pharmaceutics and Drug Delivery Systems (Paris, France)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 腸管吸収におけるディンプル型坐剤の有用性に関する研究:蛍光ラベル化デキストランを用いた検討2019

    • Author(s)
      谷川友亮、松本昭博、村尾聡、村上正裕
    • Organizer
      第69回日本薬学会関西支部総会・大会
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] ヤヌス微粒子及びその製造方法2020

    • Inventor(s)
      村上 正裕、松本 昭博
    • Industrial Property Rights Holder
      村上 正裕、松本 昭博
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-124921
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] ナノ粒子の製造方法2019

    • Inventor(s)
      村上正裕、松本昭博
    • Industrial Property Rights Holder
      村上正裕、松本昭博
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-017631
    • Filing Date
      2019
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2023-03-23  

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