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Refined structural analysis and mechanical property of drug nano-formulation by AFM in aqueous meida

Research Project

Project/Area Number 16K08190
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Physical pharmacy
Research InstitutionChiba University

Principal Investigator

MORIBE KUNIKAZU  千葉大学, 大学院薬学研究院, 教授 (50266350)

Co-Investigator(Kenkyū-buntansha) 東 顕二郎  千葉大学, 大学院薬学研究院, 准教授 (40451760)
植田 圭祐  千葉大学, 大学院薬学研究院, 助教 (40755972)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords原子間力顕微鏡(AFM) / ナノ粒子 / 力学特性 / 構造評価 / 透過型電子顕微鏡(TEM) / 原子間力顕微鏡(AFM / ポリマー / NMR / 液中測定 / AFM / ナノ
Outline of Final Research Achievements

Preparation of liposome formulation and characterization: Effect of drug-loading conditions (amount/temperature/time) on morphology of doxorubicin (DOX)-loaded liposomes was characterized by AFM and cryoTEM. No only spherical but also prolate, oblate, and concave liposomes were formed with the enhanced DOX concentration. Not only liposomal morphologies in solution but also the difference of the mechanical properties were also evaluated by AFM force curve analysis
Preparation of drug nano-formulation and characterization: Effects of drug sturucture, crystal form, and the dispersed states in excipients on the drug nanoparticle formation were evaluated by using atomic force microscopy as well as the other physicochemical evaluation techniques.

Academic Significance and Societal Importance of the Research Achievements

ナノ医薬品製剤の物性評価方法は、動的光散乱測定による平均粒子径・粒子径分布計測、SEMやTEMといった電子顕微鏡による形態観察が殆どである。後者は測定試料調製の際の乾燥や凍結により形態が変化しないナノ製剤には適用可能であるが、形態が変化したり崩壊したりする粒子も存在する。AFMによるナノ粒子の液中計測はリポソームが大半である。多くの場合、医薬品は未封入で構造や力学特性の評価も十分とはいえない。AFMを用いた液中計測による精密構造解析及び力学特性評価を各種ナノ医薬品製剤に展開することで、各種ナノ製剤毎の品質を確保する上で考慮すべき因子が明らかになる。

Report

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

    (18 results)

All 2019 2018 2017 2016 Other

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Acknowledgement Compliant: 1 results) Presentation (13 results) (of which Int'l Joint Research: 4 results,  Invited: 8 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Cryo-TEM and AFM Observation of the Time-Dependent Evolution of Amorphous Probucol Nanoparticles Formed by the Aqueous Dispersion of Ternary Solid Dispersions.2019

    • Author(s)
      Zhao Z, Katai H, Higashi K, Ueda K, Kawakami K, Moribe K
    • Journal Title

      Mol Pharm

      Volume: 印刷中 Issue: 5 Pages: 2184-2198

    • DOI

      10.1021/acs.molpharmaceut.9b00158

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Determination of Nonspherical Morphology of Doxorubicin-Loaded Liposomes by Atomic Force Microscopy.2018

    • Author(s)
      Takahashi N, Higashi K, Ueda K, Yamamoto K, Moribe K.
    • Journal Title

      J Pharm Sci.

      Volume: 107 Issue: 2 Pages: 717-726

    • DOI

      10.1016/j.xphs.2017.10.009

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Composition-dependent structural changes and antitumor activity of ASC-DP/DSPE-PEG nanoparticles.2016

    • Author(s)
      Higashi, K., Mibu, F., Saito, K., Limwikrant, W., Yamamoto, K., Moribe, K.
    • Journal Title

      Eur. J. Pharm. Sci.

      Volume: 99 Pages: 24-31

    • DOI

      10.1016/j.ejps.2016.11.029

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Eudragit Eの液中構造が薬物可溶化能に及ぼす影響2018

    • Author(s)
      岡本 裕太、植田 圭祐、東 顕二郎、森部 久仁一
    • Organizer
      日本薬剤学会 製剤創剤セミナー
    • Related Report
      2018 Annual Research Report
  • [Presentation] 分子製剤学の視点に基づく医薬品の構造及び機構解明2018

    • Author(s)
      森部久仁一
    • Organizer
      薬の未来を考える記念シンポジウム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Application of AFM for structural and morphological evaluation of drug-incorporated nanoparticles2017

    • Author(s)
      Moribe, K., Egami, K., Takahashi, N., Ueda K., Higashi, K.
    • Organizer
      Gordon Research Conference
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] AFMを用いた水溶液中におけるEudragit® Eのナノ構造体評価2017

    • Author(s)
      岡本 裕太, 植田 圭祐, 東 顕二郎, 森部 久仁一
    • Organizer
      第61回日本薬学会関東支部大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 微粒子製剤の調製と構造評価2017

    • Author(s)
      森部久仁一
    • Organizer
      特別講演会「DDSの現状と将来」
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 機能性製剤の開発に貢献する添加剤2017

    • Author(s)
      森部 久仁一
    • Organizer
      第16回 医薬品添加剤セミナー
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Supersaturation strategy for enhanced absorption of poorly water-soluble drugs2016

    • Author(s)
      Moribe, K.
    • Organizer
      2nd Int. Seminar Pharm. Sci. Tech
    • Place of Presentation
      Jatinangor, Indonesia
    • Year and Date
      2016-11-24
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] AFM observation of morphological changes of doxorubicin-loaded liposomes2016

    • Author(s)
      東 顕二郎, 高橋 尚樹, 植田 圭祐, 山本 恵司, 森部 久仁一
    • Organizer
      第59回顕微鏡学会シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2016-11-18
    • Related Report
      2016 Research-status Report
  • [Presentation] Supersaturation strategy for enhanced absorption of poorly water-soluble drugs2016

    • Author(s)
      Moribe, K.
    • Organizer
      FAPA2016
    • Place of Presentation
      Bangkok, Thaniland
    • Year and Date
      2016-11-09
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Effect of solid properties on drug dissolution from the solid formulation2016

    • Author(s)
      Moribe, K.
    • Organizer
      Asian Graduate Congress on Pharmaceutical Technology
    • Place of Presentation
      Singapore, Singapore
    • Year and Date
      2016-07-10
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] AFM及びcryo-TEMを用いたドキソルビシン封入リポソームの形態評価2016

    • Author(s)
      森部 久仁一、高橋 尚希、植田 圭祐、東 顕二郎、山本 恵司
    • Organizer
      第32回日本DDS学会学術集会
    • Place of Presentation
      静岡
    • Year and Date
      2016-06-30
    • Related Report
      2016 Research-status Report
  • [Presentation] 機能性製剤の創製に貢献する添加物2016

    • Author(s)
      森部 久仁一
    • Organizer
      第43回 日本毒性学会学術年会
    • Place of Presentation
      名古屋
    • Year and Date
      2016-06-29
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 固体分散体からの薬物溶出に影響を及ぼす因子2016

    • Author(s)
      森部 久仁一
    • Organizer
      オレオナノサイエンス部会シンポジウム2016
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report
    • Invited
  • [Book] ナノ結晶化技術の基礎と医薬品開発の現状, 難水溶性薬物の経口製剤化技術最前線2016

    • Author(s)
      東顕二郎, 森部久仁一(分担)
    • Publisher
      シーエムシー出版
    • Related Report
      2016 Research-status Report
  • [Remarks] http://www.p.chiba-u.jp/lab/seizai/

    • Related Report
      2018 Annual Research Report

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

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