Development of drug delivery system using intravital transporter protein.

2011 Fiscal Year Final Research Report

• Project/Area Number: 21500428
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomedical engineering/Biological material science
• Research Institution: Osaka Prefecture University
• Principal Investigator: TAKASHI Inui 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: DDS / 輸送タンパク質 / 難水溶性薬剤

Research Abstract

Lipocalin-type prostaglandin D synthase(L-PGDS) could improve the solubility of a poorly water-soluble compound, diazepam(DZP), a major anxiolytic drug in aqueous solutions. The oral administration of DZP/L-PGDS complex significantly extended the duration of loss of righting reflex in mice under a pentobarbital-induced anesthesia as compared with that of DZP in carboxymethylcellulose(CMC). These results demonstrate that L-PGDS is a beneficial delivery vehicle for poorly water-soluble compounds. This novel DDS will facilitate the pharmaceutical and clinical developments of various water-insoluble compounds.

Research Products

• [Journal Article] Drug delivery system for poorly water-soluble compounds using lipocalin-type prostaglandin D synthase (2012)
  • 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.
  • 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.
  • 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.
  • 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.
  • Journal Title: J. Struct. Biol. Volume: 169巻 Pages: 209-218
  • Peer Reviewed
• [Presentation] 癌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DDS (2010)
  • Author(s): 乾隆
  • Organizer: 近畿バイオインダストリー振興会議
  • 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 ischemia (2009)
  • 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
• [Remarks] ホームページ情報
  • 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