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2011 Fiscal Year Final Research Report

Development of intelligent-type drug delivery system by transporter protein.

Research Project

  • PDF
Project/Area Number 21200076
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)

Allocation TypeSingle-year Grants
Research Field Physical pharmacy
Applied pharmacology
Research InstitutionOsaka Prefecture University

Principal Investigator

INUI Takashi  大阪府立大学, 大学院生命環境科学研究科, 教授 (80352912)

Co-Investigator(Kenkyū-buntansha) NAKAJIMA Hidemitsu  大阪府立大学, 大学院・生命環境科学研究科, 准教授 (30405360)
Project Period (FY) 2009 – 2011
Keywordsドラッグデリバリーシステム / がんターゲット / 難水溶性抗がん剤 / 生体内輸送蛋白質
Research Abstract

We generated NGR (Asn-Gly-Arg)-lipocalin-type prostaglandin D synthase (L-PGDS), possessing tumor-targeting NGR-motif, which specifically binds to CD13 receptor expressing in the endothelium of angiogenic blood vessels. NGR-L-PGDS was complexed with SN-38 which is a poorly water-soluble antitumor drug. The solubility of SN-38 in the presence of 2 mM NGR-L-PGDS in PBS increased by 300-fold as compared with that in PBS. Intravenous administration of SN-38/NGR-L-PGDS complex dominantly inhibited tumor growth as compared with control in mouse xenograft tumor model using human colon cancer cells.

  • Research Products

    (22 results)

All 2012 2011 2010 2009 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (13 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Drug delivery system for poorly water-soluble compounds using lipocalin-type prostaglandin D synthase2012

    • Author(s)
      Fukuhara, A., Nakajima, H., Miyamoto, Y., Inoue, K., Kume, S., Lee, YH., Noda, M., Uchiyama, S., Shimamoto, S., Nishimura, S., Ohkubo, T., Goto, Y., Takeuchi, T., and Inui, T. (correspondence author)
    • Journal Title

      J. Control. Release

      Volume: 159 巻 Pages: 143-150

    • Peer Reviewed
  • [Journal Article] Lipocalin-type prostaglandin D synthase protects against oxidative stress-induced neuronal cell death.2012

    • Author(s)
      Fukuhara, A., Yamada, M., Fujimori, K., Kusumoto, T., Nakajima, H., and Inui, T. (correspondence author)
    • Journal Title

      Biochem. J.

      Volume: 443 巻 Pages: 75-84

    • Peer Reviewed
  • [Journal Article] NMR and CD analysis of an intermediate state in the thermal unfolding process of mouse lipocalin-type prostaglandin D synthase.2012

    • Author(s)
      Miyamoto, Y., Noda, Y., Iida, T., Yamaguchi, K., Nishimura, S., Tanaka, A., Segawa, S., and Inui, T. (correspondence author)
    • Journal Title

      J. Biochem.

      Volume: 151 巻 Pages: 335-342

    • Peer Reviewed
  • [Journal Article] Prevention of paraquat-induced apoptosis in human neuronal SH-SY5Y cells by lipocalin-type prostaglandin D synthase.2012

    • Author(s)
      Fujimori, K., Fukuhara, A., Inui, T., and Allhorn, M.
    • Journal Title

      J. Neurochem.

      Volume: 120 巻 Pages: 279-291

    • Peer Reviewed
  • [Journal Article] Structural analysis of lipocalin-type prostaglandin D synthase complexed with biliverdin by small-angle X-ray scattering and multi-dimensional NMR.2010

    • Author(s)
      Miyamoto, Y., Nishimura, S., Inoue, K., Shimamoto, S., Yoshida, T., Fukuhara, A., Yamada, M., Urade, Y., Yagi, N., Ohkubo, T., and Inui, T. (correspondence author)
    • Journal Title

      J. Struct. Biol.

      Volume: 169 巻 Pages: 209-218

    • Peer Reviewed
  • [Journal Article] GAPDH aggregate formation participates in oxidative stress-induced cell death.2009

    • Author(s)
      Nakajima, H., Amano, W., Kubo, T., Fukuhara, A., Ihara, H., Azuma, Y., Tajima, H., Inui, T., Sawa, A., and Takeuchi, T.
    • Journal Title

      J. Biol. Chem.

      Volume: 284 巻 Pages: 34331-34341

    • Peer Reviewed
  • [Presentation] がんターゲッティング機能を有するインテリジェント型薬剤輸送蛋白質を用いたSN-38 のドラッグデリバリーシステム2011

    • Author(s)
      河野正樹, 福原彩乃, 山田晃平, 井上遥, 久米慧嗣, 城田涼子, 李映昊, 後藤祐児, 乾 隆
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      国立京都国際会館 (京都)
    • Year and Date
      20110922-23
  • [Presentation] Drug Delivery System for Poorly Water-soluble Compounds Using Lipocalin Protein.2011

    • Author(s)
      Fukuhara, A., Nakajima, H., Miyamoto, Y., Kume, S., Lee, YH., Noda, M., Uchiyama, S., Ohkubo, T., Goto, Y. and Inui, T.
    • Organizer
      The 25th Annual Symposium of The Protein Society
    • Place of Presentation
      Boston Marriott Copley Place (Boston, USA)
    • Year and Date
      2011-07-25
  • [Presentation] 難水溶性薬物の経口投与におけるリポカリン蛋白質の効果2011

    • Author(s)
      福原彩乃, 久米慧嗣, 河野正樹, 人見麻衣, 李映昊, 後藤祐児, 中嶋秀満, 乾 隆
    • Organizer
      第27回日本DDS 学会学術集会
    • Place of Presentation
      東京大学本郷キャンパス (東京)
    • Year and Date
      2011-06-09
  • [Presentation] リポカリン蛋白質を用いた難水溶性薬剤に対するドラッグ・デリバリー・システムの開発2011

    • Author(s)
      福原彩乃, 中嶋秀満, 宮本優也, 久米慧嗣, 李映昊, 野田勝紀, 内山進, 西村重徳, 大久保忠恭, 後藤祐児, 乾 隆
    • Organizer
      第11 回日本蛋白質科学会年会
    • Place of Presentation
      ホテル阪急エキスポパーク(大阪)
    • Year and Date
      2011-06-08
  • [Presentation] 生体内輸送蛋白質のドラッグデリバリーシステムへの応用2010

    • Author(s)
      乾 隆
    • Organizer
      第46 回熱測定討論会
    • Place of Presentation
      三重大学(三重)
    • Year and Date
      20100927-29
  • [Presentation] Drug Delivery System for Poorly Water-soluble Drugs by Lipocalin-type Prostaglandin D Synthase.2010

    • Author(s)
      Fukuhara, A., Nakajima, H., Inoue, K., Miyamoto, Y., Shimamoto, S., Nishimura, S., Ohkubo, T., Takeuchi, T., Inui, T.
    • Organizer
      The 24^<th> Annual Symposium of The Protein Society
    • Place of Presentation
      California, USA
    • Year and Date
      20100801-05
  • [Presentation] リポカリン蛋白質を用いた難水溶性薬剤に対する新規DDS2010

    • Author(s)
      乾 隆
    • Organizer
      近畿バイオインダストリー振興会議, 第25 回 技術シーズ公開会
    • Place of Presentation
      大阪科学技術センター(大阪)
    • Year and Date
      2010-12-06
  • [Presentation] 輸送蛋白質を用いた難水溶性薬剤に対するDDS の開発-X 線小角散乱による蛋白質・薬剤複合体の構造解析2010

    • Author(s)
      乾 隆
    • Organizer
      SPring-8 利用推進協議会, 第11 回蛋白質企業研究会
    • Place of Presentation
      大型放射光施設(Spring-8)普及棟(兵庫)
    • Year and Date
      2010-11-16
  • [Presentation] 生体内輸送蛋白質を用いた難水溶性薬剤に対する新規ドラッグデリバリーシステムの開発2010

    • Author(s)
      乾 隆
    • Organizer
      大阪大学蛋白質研究所セミナー
    • Place of Presentation
      大阪大学(大阪)
    • Year and Date
      2010-10-21
  • [Presentation] Protective effect of lipocalin-type prostaglandin D synthase/NBQX complex on neuronal cell death induced by cerebral ischemia2009

    • Author(s)
      Fukuhara, A., Nakajima, H., Inoue, K., Miyamoto, Y., Nishimura, S., Yagi, N., Takeuchi, T., Inui, T.
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド(兵庫)
    • Year and Date
      20091021-24
  • [Presentation] 生体内輸送蛋白質を用いた難水溶性薬剤に対する新規DDS の開発2009

    • Author(s)
      乾 隆
    • Organizer
      第8回国際バイオフォーラム
    • Place of Presentation
      東京ビックサイト(東京)
    • Year and Date
      20090701-03
  • [Presentation] Protective effect of lipocalin-type prostaglandin D synthase on oxidative stress-induced apoptosis in SH-SY5Y cells.2009

    • Author(s)
      Fukuhara, A., Yamada, M., Kusumoto, T. Nakajima, H., Nishimura, S., and Inui, T.
    • Organizer
      VIII European Symposium of The Protein Society
    • Place of Presentation
      Zurich, Switzerland
    • Year and Date
      20090614-18
  • [Presentation] ヒトリポカリン型プロスタグランジンD 合成酵素の熱変性過程の解析2009

    • Author(s)
      飯田津喜美, 宮本優也, 深田はるみ, 田中晶善, 裏出良博, 乾 隆
    • Organizer
      第9 回日本蛋白質科学会
    • Place of Presentation
      熊本
    • Year and Date
      20090520-22
  • [Remarks]

    • URL

      http://www.bioinfo.osakafu-u.ac.jp/~inuit/

  • [Patent(Industrial Property Rights)] DDS カプセル用蛋白質およびそれを用いた薬剤とその調整方法2012

    • Inventor(s)
      乾 隆
    • Industrial Property Rights Holder
      大阪府立大学
    • Industrial Property Number
      特許, 特願2012-027389 号
    • Filing Date
      2012-02-10
  • [Patent(Industrial Property Rights)] 標的結合部を有する薬剤運搬体2010

    • Inventor(s)
      乾 隆
    • Industrial Property Rights Holder
      大阪府立大学
    • Industrial Property Number
      特許, 特願2010-078300 号
    • Filing Date
      2010-03-30

URL: 

Published: 2013-07-31  

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