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Development of bubble preparation for ultrasound theranostics

Research Project

Project/Area Number 16H03196
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical systems
Research InstitutionTeikyo University

Principal Investigator

Maruyama Kazuo  帝京大学, 薬学部, 教授 (30130040)

Co-Investigator(Kenkyū-buntansha) 茅沼 秀樹  麻布大学, 獣医学部, 講師 (10329196)
金井 詠一  麻布大学, 獣医学部, 助教 (20632219)
高瀬 有加里  帝京大学, 公私立大学の部局等, 教務職員 (80718057)
小俣 大樹  帝京大学, 薬学部, 助教 (80803113)
鈴木 亮  帝京大学, 薬学部, 准教授 (90384784)
小田 雄介  帝京大学, 薬学部, 助手 (80505941)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2016: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Keywordsマイクロバブル / 超音波 / セラノスティクス / 腫瘍新生血管 / 血液脳関門 / DDS / 超音波造影 / 超音波診断と治療 / 低侵襲治療システム / 超音波セラノスティクス
Outline of Final Research Achievements

We succeeded in the development of theranostic bubble preparation in this research. The bubble formulation is composed of DSPC:DSPG:DSPE-PEG2000(30:60:10 (molar ratio)) and contains perfluoropropane gas. The average particle size is 1 to 2 um. Blood vessel permeability enhancement by bubble preparation and ultrasound was examined in the mouse ear. Evan's blue emission was observed. The therapeutic effect was obtained from the experiment of delivery of DOXIL to dogs with thyroid cancer. In addition to blood flow imaging with contrast-enhanced ultrasound, the developed bubble preparation was able to open the blood vessel by oscillation with therapeutic ultrasound irradiation and deliver the drug. This research is the first in the world to develop a theranostic bubble formulation.

Academic Significance and Societal Importance of the Research Achievements

国民の4人に1人が 65 歳以上となる超高齢化社会に入った我が国において、高齢者疾患の原因臓器・細胞を標的とする画期的な薬物治療法の開発は急務である。画期的なシステムとしてtherapeutics(治療)とdiagnostics(診断)の両機能を有するセラノスティクス(Theranostics)が注目されている。本研究でセラノスティクスバブル製剤の開発に成功した。開発されたバブル製剤は、造影超音波による血流造影だけでなく、治療超音波照射によるオシレーションによって、照射部位でのみ血管をオープニングさせ、薬物を送達出来る。セラノスティクスバブル製剤の開発は世界でも本研究が最初である

Report

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

    (22 results)

All 2019 2018 2017 2016

All Journal Article (5 results) (of which Peer Reviewed: 3 results,  Open Access: 5 results) Presentation (17 results) (of which Int'l Joint Research: 6 results,  Invited: 12 results)

  • [Journal Article] Ultrasound-responsive nanobubble-mediated gene transfection in the cerebroventricular region by intracerebroventricular administration in mice.2019

    • Author(s)
      Koki Ogawa, Yuki Fuchigami, Masayori Hagimori, Kazuo Maruyama, Shintaro Fumoto, Shigeru Kawakami.
    • Journal Title

      Euro. J. of Pharmaceutics and Biopharmaceutics

      Volume: 173 Pages: 1-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development and evaluation of stability and ultrasound response of DSPC-DPSG-based freeze-dried microbubbles.2018

    • Author(s)
      Johan Unga, Daiki Omata, Nobuki Kudo, Soki Ueno, Lisa Munakata, Tadamitsu Shima, Ryo Suzuki and Kazuo Maruyama
    • Journal Title

      J. Liposome Res.

      Volume: 10 Pages: 1-27

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acoustic field sweeping for active induction of bubble-surrounded T-cells2018

    • Author(s)
      Oitate Riki、Otsuka Takuya、Seki Masakazu、Furutani Asuka、Mochizuki Takashi、Masuda Kohji、Suzuki Ryo、Maruyama Kazuo
    • Journal Title

      Japanese Journal of Applied Physics

      Volume: 57 Issue: 7 Pages: 07LF10-07LF10

    • DOI

      10.7567/jjap.57.07lf10

    • NAID

      210000149347

    • URL

      https://localhost/en/publications/459e9c84-8547-43e3-acea-e05f7014416a

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] マイクロバブルを用いた超音波セラノスティクス2017

    • Author(s)
      丸山一雄
    • Journal Title

      細胞

      Volume: 49 Pages: 581-584

    • Related Report
      2017 Annual Research Report
    • Open Access
  • [Journal Article] リピッドバブルと超音波によるセラノスティクスシステム2017

    • Author(s)
      丸山一雄
    • Journal Title

      日本音響学会誌

      Volume: 73 Pages: 1-8

    • NAID

      130006301015

    • Related Report
      2017 Annual Research Report
    • Open Access
  • [Presentation] マイクロバブルと超音波による革新的薬物送達技術2018

    • Author(s)
      丸山一雄
    • Organizer
      第7回超異分野学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Enhancement of ERP effect by the combination of lipid bubbles and ultrasound2018

    • Author(s)
      Kazuo Maruyama, Johan Unga, Daiki Omata, Ryo Suzuki
    • Organizer
      11th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] リピッドバブルと超音波によるセラノスティクスと遺伝子デリバリー2018

    • Author(s)
      丸山一雄, 鈴木亮, 小俣大樹, 高橋葉子, 根岸洋一
    • Organizer
      日本薬学会第138年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ENHANCEMENT OF EPR EFFECT AND DRUG DELIVERY BY THE COMBINATION OF NEW LIPID BUBBLES AND ULTRASOUND.2018

    • Author(s)
      Kazuo Maruyama, Johan Unga, Daiki Omata, Tomohiro Osaki, Ryo Suzuki
    • Organizer
      18th International Symposium on therapeutic ultrasound (ISTU2018).
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] リピッドバブルと超音波による血管透過性亢進に基づくEPR効果促進2018

    • Author(s)
      丸山一雄
    • Organizer
      日本薬剤学会第33年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 超音波セラノスティックシステムの実用化を目指す研究拠点形成2018

    • Author(s)
      丸山一雄
    • Organizer
      第62回日本薬学会関東支部大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Enhancement of EPR effect in drug delivery by the combination of lipid bubbles and ultrasound2018

    • Author(s)
      Kazuo Maruyama.Ryo Suzuki
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Enhancement of drug delivery to tumor tissue by the combination of lipidbubbles and ultrasound.2018

    • Author(s)
      Kazuo Maruyama
    • Organizer
      13th France-Japan Drug Delivery Systems Symposium.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ドラッグデリバリーシステムにおける超音波医療技術の最先端2018

    • Author(s)
      丸山一雄
    • Organizer
      第17回日本超音波治療研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] BUS-DDS(Bubble-Ultrasound mediated DDS)血管壁を開口して薬の届かない所に届けて効かせる2018

    • Author(s)
      丸山一雄
    • Organizer
      第4回超音波分子診断治療研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 超音波セラノスティクスへの応用を目的とした新規血中安定型バブル製剤の創製2017

    • Author(s)
      杉井むつみ、鈴木亮、小田雄介、Johan Unga、宇留賀仁史、小俣大樹、丸山一雄
    • Organizer
      第32回 日本DDS学会
    • Place of Presentation
      京都 The Westin Miyako Kyoto (Japan)
    • Year and Date
      2017-02-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] Non-Viral Gene Delivery Systems by the Combination of Lipid Bubbles and Ultrasound: Applications in siRNA, mRNA, Plasmid DNA2017

    • Author(s)
      Kazuo Maruyama
    • Organizer
      9th Annual AsiaTIDES
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 新規マイクロバブルを用いたがんの診断/治療2017

    • Author(s)
      大崎智弘、村端悠介、鈴木亮、丸山一雄
    • Organizer
      日本超音波医学会第90回学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Ultrasound Theranostics for Tumor2017

    • Author(s)
      Kazuo Maruyama
    • Organizer
      ISTU Symposium , 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 超音波セラノスティクス用バブル製剤の開発2017

    • Author(s)
      丸山一雄、Johan Unga、小俣大樹、 鈴木亮
    • Organizer
      第16回日本超音波治療研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 超音波セラノスティクス ―リピッドバブルと超音波による癌新生血管の造影と開口によるEPR効果の亢進―2017

    • Author(s)
      丸山一雄
    • Organizer
      日本薬学会関東支部第42回学術講演会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] DEVELOPMENT OF A NEW LIPID BUBBLE FOR ULTRASOUND THERANOSTICS2016

    • Author(s)
      Kazuo Maruyama
    • Organizer
      12th France -Japan Drug Delivery Systems Symposium
    • Place of Presentation
      Abbaye des Vaux de Cernay (France)
    • Year and Date
      2016-10-09
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2016-04-21   Modified: 2022-12-28  

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