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Development of a macromolecular prodrug for the treatment of bone

Research Project

Project/Area Number 16H03185
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionKansai University

Principal Investigator

Iwasaki Yasuhiko  関西大学, 化学生命工学部, 教授 (90280990)

Co-Investigator(Kenkyū-buntansha) 上田 正人  関西大学, 化学生命工学部, 教授 (40362660)
Research Collaborator NOREE Susita  
INOUE Naoyuki  
HIRANO Yuya  
KUNOMURA Shun  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywordsポリリン酸エステル / 生分解性 / 骨 / 骨リモデリング / プロドラッグ / 開環重合 / 生体適合性 / 生体模倣 / 骨治療 / 生分解性ポリマー / ドラッグデリバリーシステム / 骨系細胞 / 骨転移 / 骨疾患治療 / ポリマー医薬 / 薬物輸送 / 破骨細胞 / 骨芽細胞 / ミネラリゼーション / 体内動態
Outline of Final Research Achievements

In the present study, we evaluated the effects of poly(ethylene sodium phosphate) (PEPNa), which is a kind of polyhpsphoesters (PPEs), on bone cell viability and activity. PEPNa exhibited excellent short-term biocompatibility with osteoblasts. In contrast, selective inhibition of osteoclast adhesion and function was observed following cultivation with PEPNa. Moreover, we have demonstrated that PEPNa shows good affinity for bone in vivo. Due to the molecular diversity of PPEs, various types of polymeric prodrugs for bone disease treatment can be designed based on PEPNa.

Academic Significance and Societal Importance of the Research Achievements

本研究課題の遂行により骨親和性と骨リモデリングに作用するポリマーを新たに提案することができた。このポリマーは我が国が抱えている社会的な課題である健康寿命の増進に資することが期待され、研究成果の社会的意義は極めて大きいと言える。また、これまでのプロドラッグ設計では生体不活性なポリマーと薬剤を複合化する手法が取られていたが、本研究で得られたポリマーは生理活性を示すため学術的にもユニークであり、同ポリマーを用いたプロドラック研究が今後多く展開されると思われる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (41 results)

All 2019 2018 2017 2016 Other

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (29 results) (of which Int'l Joint Research: 13 results,  Invited: 7 results) Book (1 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Immobilization of polyphosphoesters on poly(ether ether ketone) (PEEK) for facilitating mineral coating2019

    • Author(s)
      Shun Kunomura, Yasuhiko Iwasaki
    • Journal Title

      J. Biomater. Sci., Polym. Edn.

      Volume: in press Issue: 10 Pages: 861-876

    • DOI

      10.1080/09205063.2019.1595305

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endocytosis of poly(ethylene sodium phosphate) by macrophages and the effect of polymer length on cellular uptake2019

    • Author(s)
      Akihisa Otaka, Yasuhiko Iwasaki
    • Journal Title

      J. Ind. Eng. Chem.

      Volume: 75 Pages: 115-122

    • DOI

      10.1016/j.jiec.2019.03.010

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Thermally assisted generation of protein-poly(ethylene sodium phosphate) conjugates with high mineral affinity2019

    • Author(s)
      Suita Norte, Yasuhiko Iwasaki
    • Journal Title

      ACS Omega

      Volume: 4 Issue: 2 Pages: 3398-3404

    • DOI

      10.1021/acsomega.8b03585

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bone-specific poly(ethylene sodium phosphate)-bearing biodegradable nanoparticles2017

    • Author(s)
      Hirano Yuya、Iwasaki Yasuhiko
    • Journal Title

      Colloids and Surfaces B: Biointerfaces

      Volume: 153 Pages: 104-110

    • DOI

      10.1016/j.colsurfb.2017.02.015

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intelligent Polyphosphoester-Based Biomaterials2017

    • Author(s)
      IWASAKI Yasuhiko
    • Journal Title

      KOBUNSHI RONBUNSHU

      Volume: 74 Issue: 3 Pages: 172-181

    • DOI

      10.1295/koron.2016-0067

    • NAID

      130005678950

    • ISSN
      0386-2186, 1881-5685
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone-targeting poly(ethylene sodium phosphate).2017

    • Author(s)
      Iwasaki Y, Yokota A, Otaka A, Inoue N, Yamaguchi A, Yoshitomi T, Yoshimoto K, Neo M.
    • Journal Title

      Biomater Sci.

      Volume: 6 Issue: 1 Pages: 91-95

    • DOI

      10.1039/c7bm00930e

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antimicrobial silver nanoclusters bearing biocompatible phosphorylcholine based zwitterionic protects2016

    • Author(s)
      A. Sangsuwan, H. Kawasaki, Y. Matsumura, Y. Iwasaki
    • Journal Title

      Bioconjugate Chemistry

      Volume: 27 Issue: 10 Pages: 2527-2533

    • DOI

      10.1021/acs.bioconjchem.6b00455

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Heat-induced nanocomplexation of proteins with amphiphilic poly(ethylene sodium phosphate)2018

    • Author(s)
      Susita Noree, Yasuhiko Iwasaki
    • Organizer
      ICAPPP2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 骨転移がん治療を目指した骨指向性リン脂質ポリマー2018

    • Author(s)
      大高晋之, 山口知己, 平賀徹, 岩﨑泰彦
    • Organizer
      第40回日本バイオマテリアル学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 骨親和性ポリリン酸エステルと破骨細胞との相互作用2018

    • Author(s)
      岩﨑泰彦, 大高晋之, 中村美穂, 横田淳司, 根尾昌志
    • Organizer
      第40回日本バイオマテリアル学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Polyphosphoesters as a versatile framework for polymeric biomaterials2018

    • Author(s)
      Yasuhiko Iwasaki
    • Organizer
      2018GCBME
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Bone targeting polyphosphoesters as antiresorptive agents2018

    • Author(s)
      Yasuhiko Iwasaki
    • Organizer
      International Conference on Emerging Healthcare Materials 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Design of thermally-assisted complexation of proteins with amphiphilic poly(ethylene sodium phosphate)2018

    • Author(s)
      Susita Noree, Yasuhiko Iwasaki
    • Organizer
      第67回高分子討論会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ポリリン酸エステルを用いたマクロファージ指向性薬剤2018

    • Author(s)
      大高晋之,岩﨑泰彦
    • Organizer
      第67回高分子討論会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Polyphosphoesters as a versatile platform for polymeric biomaterials2018

    • Author(s)
      Yasuhiko Iwasaki
    • Organizer
      14th Japan-Belgium Symposium on Polymer Science
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] リン含有バイオミメティックポリマーの合成と機能―血液適合性表面の設計から骨リモデリングの制御まで―2018

    • Author(s)
      岩﨑泰彦
    • Organizer
      第27回日本次世代人工腎臓研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Bone-targeting polyphosphoesters and their interaction with bone cells2018

    • Author(s)
      Yasuhiko Iwasaki, Atsushi Yokota, Akihisa Otaka, Masashi Neo
    • Organizer
      256th ACS National Meeting & Exposition
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Thermally assisted complexation of proteins with amphiphilic poly(ethylene sodium phosphate) as versatile excipients2018

    • Author(s)
      Susita Noree, Yasuhiko Iwasaki
    • Organizer
      第47回医用高分子シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 難溶性抗がん剤を可溶化する骨指向性リン脂質ポリマー2018

    • Author(s)
      大高晋之,山口知己,平賀徹,岩﨑泰彦
    • Organizer
      第47回医用高分子シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] ポリリン酸エステルの細胞内取り込みが破骨細胞に与える影響2018

    • Author(s)
      大高晋之,中村美穂,岩﨑泰彦
    • Organizer
      第64回高分子研究発表会(神戸)
    • Related Report
      2018 Annual Research Report
  • [Presentation] Bone-targeting phospholipid polymer to solubilize lipophilic anticancer drug2018

    • Author(s)
      Akihisa Otaka, Tomoki Yamaguchi, Toru Hiraga, Yasuhiko Iwasaki
    • Organizer
      Finland-Japan Workshop: The next generation medical engineering in biomaterials
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Suppression of heat-induced denaturation of proteins via complexation with amphiphilic poly(ethylene sodium phosphate)2018

    • Author(s)
      Susita Noree, Yasuhiko Iwasaki
    • Organizer
      第67回高分子年次大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ポリリン酸エステルのマクロファージ取込み能評価2018

    • Author(s)
      大高晋之, 岩﨑泰彦
    • Organizer
      第67回高分子年次大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Polyphosphoesters: Modern synthesis and new therapeutic agents for the treatment of bone2018

    • Author(s)
      Yasuhiko Iwasaki
    • Organizer
      International Biomaterials Symposium at Clemson University
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cellular interaction and bone affinity of poly(ethylene sodium phosphate)2018

    • Author(s)
      Yasuhiko Iwasaki, Atsushi Yokota, Akihisa Otaka, Masashi Neo
    • Organizer
      Society for Biomaterials 2018 Annual Meeting and Exposition
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 超生体機能を実現するバイオマテリアルデザイン2017

    • Author(s)
      岩﨑泰彦
    • Organizer
      日本歯科理工学会平成29年度近畿・中四国地方会夏期セミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] タイコ酸模倣ポリリン酸ポリマーの分子量がマクロファージ食作用に与える影響2017

    • Author(s)
      大高晋之 ,井上直之 ,岩﨑泰彦
    • Organizer
      日本バイオマテリアル学会関西ブロック 第 12 回若手研究発表会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Low‐temperature processable biodegradable block copolymers embedded with proteins2017

    • Author(s)
      Yasuhiko Iwasaki
    • Organizer
      6th ABMC
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] リン酸エステルポリマーのマクロファージ取込み能評価2017

    • Author(s)
      大高晋之 ,井上直之 ,岩﨑泰彦
    • Organizer
      日本バイオマテリアル学会北信越ブロック第6回若手研究発表会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Binding affinity of poly(ethylene phosphate) nanoparticles to bone2016

    • Author(s)
      Y. Hirano, H. Hongou, Y. Iwasaki
    • Organizer
      The 11th SPSJ International Polymer Conference (IPC 2016)
    • Place of Presentation
      福岡国際会議場(福岡市博多区)
    • Year and Date
      2016-12-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 骨治療に向けたポリリン酸エステルの分子デザイン2016

    • Author(s)
      岩﨑泰彦
    • Organizer
      日本バイオマテリアル学会シンポジウム2016
    • Place of Presentation
      福岡国際会議場(福岡市博多区)
    • Year and Date
      2016-11-21
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ポリリン酸エステルナノ粒子の骨の無機主成分に対する親和性に及ぼすpH の影響2016

    • Author(s)
      平野佑弥,岩﨑泰彦
    • Organizer
      第65回 高分子年次大会
    • Place of Presentation
      神戸国際会議場(神戸市中央区)
    • Year and Date
      2016-05-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] ポリエチレンホスフェートによる骨芽細胞の機能誘導2016

    • Author(s)
      井上直之,岩﨑泰彦
    • Organizer
      第65回 高分子年次大会
    • Place of Presentation
      神戸国際会議場(神戸市中央区)
    • Year and Date
      2016-05-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] Regulation of osteoclast function by poly(ethylene sodium phosphate)2016

    • Author(s)
      Y. Iwasaki, S. Kootala, J. Hilborn
    • Organizer
      10th World Biomaterials Congress
    • Place of Presentation
      モントリオール(カナダ)
    • Year and Date
      2016-05-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Preparation and characterization of polyphosphoester coated nanoparticles having a potential for delivery of hydrophobic drugs to bone2016

    • Author(s)
      Y. Hirano, Y. Iwasaki
    • Organizer
      10th World Biomaterials Congress
    • Place of Presentation
      モントリオール(カナダ)
    • Year and Date
      2016-05-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ポリリン酸エステルによる骨系細胞の機能制御2016

    • Author(s)
      井上直之,中村美穂,岩﨑泰彦
    • Organizer
      日本バイオマテリアル学会第11回関西若手研究発表会
    • Place of Presentation
      神戸大学(神戸市灘区)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Book] 刺激応答性高分子ハンドブック2018

    • Author(s)
      岩﨑泰彦
    • Total Pages
      864
    • Publisher
      NTS
    • Related Report
      2018 Annual Research Report
  • [Remarks] 関西大学 化学生命工学部 化学・物質工学科 生体材料学研究室

    • URL

      http://www.chemmater.kansai-u.ac.jp/biomat/

    • Related Report
      2018 Annual Research Report
  • [Remarks]

    • URL

      http://biomat.chemmater.kansai-u.ac.jp/index.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 関西大学 化学生命工学部 生体材料学研究室

    • URL

      http://biomat.chemmater.kansai-u.ac.jp/index.html

    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] リン酸ジエステル-リン酸トリエステル共重合体およびその合成方法ならびに骨標的薬物輸送担体2017

    • Inventor(s)
      岩﨑泰彦、大高晋之、横田淳司、根尾昌志
    • Industrial Property Rights Holder
      関西大学、大阪医科大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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