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Design of Synthetic Polymer Nanoparticles Specifically Capturing Indole for improvement of uremia symptom

Research Project

Project/Area Number 17K14519
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Bio-related chemistry
Research InstitutionUniversity of Shizuoka

Principal Investigator

Koide Hiroyuki  静岡県立大学, 薬学部, 講師 (60729177)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsナノ粒子 / 分子認識 / 低分子 / インドール / 経口投与 / 尿毒症 / ポリマーナノ粒子 / 慢性腎臓病 / 高分子 / 腎臓病 / ナノ材料
Outline of Final Research Achievements

Synthetic polymer hydrogel nanoparticles (NPs) capable of capturing and/or releasing target biomacromolecules are of interest as alternative bio-affinity ligands. In the present study, we focused on the developing NPs that adsorb indole in the intestine for chronic kidney disease (CKD) therapy.
NPs were prepared by an aqueous dispersion copolymerization of NIPAm, various hydrophobic monomers, and a cross-linker. Indole adsorption rates were significantly changed by varying the structure and percentage of the hydrophobic monomers in the NPs. However, NPs did not adsorb the indole analogs. NP inhibited intestinal absorption of indole not only in vitro but also in the biological milieu. These results suggest that usability of NPs as an epoch-making oral absorbent.

Academic Significance and Societal Importance of the Research Achievements

本研究では、尿毒症症状の悪化を抑制するために、消化管でインドールを選択的に吸着するナノ粒子の開発を行った。その結果、ナノ粒子とインドールをマウスに経口投与することで、インドールの体内蓄積率を有意に減少させることに成功した。
現在臨床で用いられている消化管での標的分子吸着材は、標的分子以外も吸着してしまうため、他の薬剤を服用してから数時間間隔をあける必要がある。さらに、栄養素も吸着してしまうため、食後数時間間隔をあける必要がある。本研究で開発したナノ粒子はこれら問題点を克服することが可能となる可能性がある。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (15 results)

All 2019 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (6 results) (of which Int'l Joint Research: 1 results) Book (2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Design of Synthetic Polymer Nanoparticles Specifically Capturing Indole, a Small Toxic Molecule.2019

    • Author(s)
      Okishima A, Koide H, Hoshino Y, Egami H, Hamashima Y, Oku N, Asai T.
    • Journal Title

      Biomacromolecules

      Volume: 20 Issue: 4 Pages: 1644-1654

    • DOI

      10.1021/acs.biomac.8b01820

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Rigorous control of vesicle-forming lipid pKa by fluorine-conjugated bioisosteres for gene-silencing with siRNA.2019

    • Author(s)
      Okamoto A, Koide H, Morita N, Hirai Y, Kawato Y, Egami H, Hamashima Y, Asai T, Dewa T, Oku N.
    • Journal Title

      J. Control. Release.

      Volume: 295 Pages: 87-92

    • DOI

      10.1016/j.jconrel.2018.12.044

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Systemic administration of siRNA with anti-HB-EGF antibody-modified lipid nanoparticles for the treatment of triple-negative breast cancer.2018

    • Author(s)
      Okamoto A, Asai T, Hirai Y, Shimizu K, Koide H, Minamino T, Oku N
    • Journal Title

      Mol Pharm.

      Volume: 15 Issue: 4 Pages: 1495-1504

    • DOI

      10.1021/acs.molpharmaceut.7b01055

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rational designing of an antidote nanoparticle decorated with abiotic polymer ligands for capturing and neutralizing target toxins.2017

    • Author(s)
      Koide H, Tsuchida H, Nakamoto M, Okishima A, Ariizumi S, Kiyokawa C, Asai T, Hoshino Y, Oku N.
    • Journal Title

      J Control Release

      Volume: 268 Pages: 335-342

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] A polymer nanoparticle with engineered affinity for a vascular endothelial growth factor (VEGF165)2017

    • Author(s)
      Hiroyuki Koide,Keiichi Yoshimatsu,Yu Hoshino,Shih-Hui Lee,Ai Okajima,Saki Ariizumi, Yudai Narita,Yusuke Yonamine,Adam C. Weisman,Yuri Nishimura,Naoto Oku,Yoshiko Miura,Kenneth J. Shea
    • Journal Title

      Nature Chemistry

      Volume: 9 Issue: 7 Pages: 715-722

    • DOI

      10.1038/nchem.2749

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 慢性腎臓病の進行抑制を指向したインドール吸着ポリマーナノ粒子の創製2018

    • Author(s)
      沖嶋杏奈、小出裕之、星野 友、江上寛通、濱島義隆、浅井知浩、奥 直人
    • Organizer
      日本薬学会第138年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 敗血症治療に向けた多官能性ポリマーナノ粒子の開発2018

    • Author(s)
      小出 裕之、星野 友、SHEA Kenneth J、奥 直人
    • Organizer
      日本薬学会第138年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 慢性腎臓病の進行抑制に向けたインドール吸着ポリマーナノ粒子の創製2018

    • Author(s)
      沖嶋杏奈、小出裕之、星野 友、江上寛通、濱島義隆、奥 直人、浅井知浩
    • Organizer
      日本薬剤学会第33年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 生体内で標的毒素を中和するリポソーム人工抗体の開発2018

    • Author(s)
      小出 裕之、土田大貴、仲本正彦、沖嶋杏奈、星野 友、奥 直人、浅井知浩
    • Organizer
      日本生化学会中部支部第82回例会・シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] Rational design of synthetic polymer nanoparticles that specifically adsorb a toxic molecule2018

    • Author(s)
      Anna Okishima, Hiroyuki Koide, Yu Hoshino, Naoto Oku, Tomohiro Asai
    • Organizer
      NANODDS 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 消化管内でインドールを吸着するポリマーナノ粒子の開発2017

    • Author(s)
      沖島杏奈、小出裕之、星野 友、江上寛通、濱島義隆、奥 直人
    • Organizer
      第66回高分子討論会
    • Related Report
      2017 Research-status Report
  • [Book] 生体内で標的高分子を吸着してその機能を中和するプラスチック抗体2018

    • Author(s)
      小出裕之、奥 直人、星野 友、三浦佳子
    • Publisher
      月刊プラスチック
    • Related Report
      2018 Annual Research Report
  • [Book] 標的分子を吸着してその機能を無毒化するプラスチック抗体開発2018

    • Author(s)
      小出裕之
    • Publisher
      化学工業
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] インドール及びその誘導体吸着剤2018

    • Inventor(s)
      小出裕之、沖嶋杏奈、星野 友、奥 直人
    • Industrial Property Rights Holder
      小出裕之、沖嶋杏奈、星野 友、奥 直人
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] インドール及びその誘導体吸着材2018

    • Inventor(s)
      小出裕之、星野 友、沖嶋杏奈、奥 直人
    • Industrial Property Rights Holder
      小出裕之、星野 友、沖嶋杏奈、奥 直人
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2020-03-30  

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