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Research for improvement of local CNS drug delivery system and its generalization

Research Project

Project/Area Number 26293319
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionTohoku University

Principal Investigator

Saito Ryuta  東北大学, 大学病院, 助教 (10400243)

Co-Investigator(Kenkyū-buntansha) 冨永 悌二  東北大学, 医学(系)研究科(研究院), 教授 (00217548)
芳賀 洋一  東北大学, その他の研究科, 教授 (00282096)
荒井 啓行  東北大学, 加齢医学研究所, 教授 (30261613)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000)
Fiscal Year 2016: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Keywords薬剤送達 / 中枢神経系 / 脳腫瘍 / アルツハイマー病 / てんかん / アルツハイマー
Outline of Final Research Achievements

Recently, we have been working towards CNS (central nervous system) drug delivery system that enables effective distribution of the infusate. Aiming at improved and stable drug delivery system, we developed ultrasound facilitated drug delivery (UFD) device that achieve improved distribution in brain parenchyma. In this study, in order to improve the system, we developed pressure-controlled microinfusion pump. We demonstrated that our system enabled constant pressure delivery within +/- 1mmHg pressure range. Second generation UFD device was also fabricated for stable delivery. Subsequently, to prove that our device is applicable to multiple CNS diseases, we attempted to deliver therapeutic agents to epilepsy model, spinal disease model, and Alzheimer disease model. Anti-epileptic agents worked in epilepsy model, chemotherapeutic drug worked in spinal tumor model. Both of these headed for publication of the literature.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (24 results)

All 2017 2016 2015 2014

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 5 results,  Acknowledgement Compliant: 6 results) Presentation (13 results) (of which Int'l Joint Research: 2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Convection-enhanced delivery of a hydrophilic nitrosourea ameliorates deficits and suppresses tumor growth in experimental spinal cord glioma models.2017

    • Author(s)
      Ogita S, Endo T, Sugiyama S, Saito R, Inoue T, Sumiyoshi A, Nonaka H, Kawashima R, Sonoda Y, Tominaga T.
    • Journal Title

      Acta Neurochir (Wien)

      Volume: 159(5) Issue: 5 Pages: 939-946

    • DOI

      10.1007/s00701-017-3123-2

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Convection-enhanced Delivery of Therapeutics for Malignant Gliomas2017

    • Author(s)
      Saito R, Tominaga T.
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 57 Issue: 1 Pages: 8-16

    • DOI

      10.2176/nmc.ra.2016-0071

    • NAID

      130005290681

    • ISSN
      0470-8105, 1349-8029
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Local convection-enhanced delivery of an anti-CD40 agonistic monoclonal antibody induces antitumor effects in mouse glioma models.2016

    • Author(s)
      Shoji T, Saito R, Chonan M, Shibahara I, Sato A, Kanamori M, Sonoda Y, Kondo T, Ishii N, Tominaga T.
    • Journal Title

      Neuro Oncol.

      Volume: 18(8) Issue: 8 Pages: 1120-8

    • DOI

      10.1093/neuonc/now023

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Temozolomide reverses doxorubicin resistance by inhibiting P-glycoprotein in malignant glioma cells.2016

    • Author(s)
      Zhang R, Saito R, Shibahara I, Sugiyama S, Kanamori M, Sonoda Y, Tominaga T.
    • Journal Title

      J Neurooncol

      Volume: 126(2) Issue: 2 Pages: 235-242

    • DOI

      10.1007/s11060-015-1968-x

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Intraparenchymal ultrasound application and improved distribution of infusate with convection-enhanced delivery in rodent and nonhuman primate brain.2016

    • Author(s)
      Mano Y, Saito R, Haga Y, Matsunaga T, Zhang R, Chonan M, Haryu S, Shoji T, Sato A, Sonoda Y, Tsuruoka N, Nishiyachi K, Sumiyoshi A, Nonaka H, Kawashima R, Tominaga T.
    • Journal Title

      J Neurosurg.

      Volume: 124(5) Issue: 5 Pages: 1490-500

    • DOI

      10.3171/2015.3.jns142152

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] roperties of convective delivery in spinal cord gray matter: laboratory investigation and computational simulations.2016

    • Author(s)
      Endo T, Fujii Y, Sugiyama SI, Zhang R, Ogita S, Funamoto K, Saito R, Tominaga T.
    • Journal Title

      J Neurosurg Spine

      Volume: vol.24 No.2 Issue: 2 Pages: 359-366

    • DOI

      10.3171/2015.5.spine141148

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Convection-enhanced delivery of SN-38-loaded polymeric micelles (NK012) enables consistent distribution of SN-38 and is effective against rodent intracranial brain tumor models.2015

    • Author(s)
      Zhang R, Saito R, Mano Y, Sumiyoshi A, Kanamori M, Sonoda Y, Kawashima R, Tominaga T.
    • Journal Title

      Drug Delivery

      Volume: 2 Issue: 8 Pages: 1-7

    • DOI

      10.3109/10717544.2015.1081994

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Intraparenchymal ultrasound application improve the distribution of convection-enhanced delivery in rodents’ and non-human primates’ brain2015

    • Author(s)
      Yui Mano, Ryuta Saito, Yoichi Haga, Tadao Matsunaga, Rong Zhang, M.D., Chonan Masashi, Shinya Haryu, Takuhiro Shoji, Aya Sato, Yukihiko Sonoda, Noriko Tsuruoka, Keisuke Nishiyachi, Akira Sumiyoshi, Hiroi Nonaka, Ryuta Kawashima, Teiji Tominaga
    • Journal Title

      Journal of Neurosurgery

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Peri-tumoral leakage during intra-tumoral convection-enhanced delivery has implications for efficacy of peri-tumoral infusion before removal of tumor.2014

    • Author(s)
      Yang X, Saito R, Nakamura T, Zhang R, Sonoda Y, Kumabe T, Forsayeth J, Bankiewicz K, Tominaga T
    • Journal Title

      Drug Delivery

      Volume: in press Issue: 3 Pages: 771-776

    • DOI

      10.3109/10717544.2014.914987

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Concentration rather than dose defines the local brain toxicity of agents that are effectively distributed by convection-enhanced delivery.2014

    • Author(s)
      Zhang R, Saito R, Mano Y, Kanamori M, Sonoda Y, Kumabe T, Tominaga T
    • Journal Title

      J Neurosci Methods

      Volume: 222 Pages: 131-137

    • DOI

      10.1016/j.jneumeth.2013.11.004

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Presentation] 脳幹部再発神経膠腫に対する塩酸ニムスチン局所投与:単施設第I相試験総括報告2016

    • Author(s)
      齋藤竜太
    • Organizer
      第34回日本脳腫瘍学会学術集会
    • Place of Presentation
      甲府富士屋ホテル
    • Year and Date
      2016-12-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] 超音波併用薬剤送達法を用いた局所投薬による脳腫瘍モデル治療効果の検討2016

    • Author(s)
      ジャ ウェンティン
    • Organizer
      第34回日本脳腫瘍学会学術集会
    • Place of Presentation
      甲府富士屋ホテル
    • Year and Date
      2016-12-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] Convection-enhanced delivery of nimustine hydrochloride (ACNU) against patients with recurrent malignant gliomas: on-going clinical trial2016

    • Author(s)
      齋藤竜太
    • Organizer
      Society for Neuro-Oncology 2016 Annual Scientific Meeting
    • Place of Presentation
      Sottsdale, Arizona, USA
    • Year and Date
      2016-11-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 超音波併用薬剤送達デバイスの開発-高効率化・安定化による効果実証-2016

    • Author(s)
      佐藤綾耶、井上憲司、齋藤竜太、Jia Wenting、奥野さおり、大橋雄二、鎌田圭、吉川彰、冨永悌二
    • Organizer
      第77回応用物理学会秋季学術講演会
    • Place of Presentation
      新潟(朱鷺メッセ)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 超音波併用薬剤送達デバイスの開発2016

    • Author(s)
      井上 憲司、佐藤 綾耶、齋藤 竜太、Jia Wenting、奥野 さおり、大橋 雄二、鎌田 圭、吉川 彰1、冨永 悌二
    • Organizer
      第77回応用物理学会秋季学術講演会
    • Place of Presentation
      新潟(朱鷺メッセ)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 脳腫瘍に対する局所化学療法:Convection-enhanced delivery2016

    • Author(s)
      齋藤竜太
    • Organizer
      第21回日本脳腫瘍の外科学会
    • Place of Presentation
      虎ノ門ヒルズフォーラム
    • Related Report
      2016 Annual Research Report
  • [Presentation] 脳幹部再発神経膠腫に対するConvection-enhanced deliveryによる塩酸ニムスチン局所投与:第I相試験2016

    • Author(s)
      齋藤竜太
    • Organizer
      日本脳神経外科学会 第75回学術総会
    • Place of Presentation
      福岡国際会議場・福岡サンパレス・マリンメッセ福岡
    • Related Report
      2016 Annual Research Report
  • [Presentation] 脊髄再発悪性神経膠腫に対する塩酸ニムスチン局所薬剤送達治療の有効性について2016

    • Author(s)
      荻田庄吾
    • Organizer
      日本脳神経外科学会 第75回学術総会
    • Place of Presentation
      福岡国際会議場・福岡サンパレス・マリンメッセ福岡
    • Related Report
      2016 Annual Research Report
  • [Presentation] onvection-enhanced delivery of nimustine hydrochloride for brainstem malignant glioma.2015

    • Author(s)
      Ryuta Saito, Teiji Tominaga.
    • Organizer
      SNO-SCIDOT Joint Conference on Therapeutic Delivery to the CNS
    • Place of Presentation
      San Antonio, USA.
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MRIモニタリング下ニトロソウレア剤Convection-enhanced deliveryによる神経膠腫新規治療法の開発2015

    • Author(s)
      齋藤竜太、園田順彦、庄司拓大、針生新也、眞野唯、長南雅志、金森政之、隈部俊宏、冨永悌二
    • Organizer
      日本脳神経外科学会 第74回学術総会
    • Place of Presentation
      北海道札幌、ロイトン札幌/札幌芸術文化の館/札幌市教育文化会館
    • Year and Date
      2015-10-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] MRIモニタリング下化学療法剤局所投与による脳幹部悪性神経膠腫の治療2015

    • Author(s)
      齋藤竜太、園田順彦、金森政之、庄司拓大、眞野唯、隈部俊宏、冨永悌二
    • Organizer
      第52 回(社)日本脳神経外科学会東北支部会
    • Place of Presentation
      福島、ホテルサンルートプラザ福島
    • Year and Date
      2015-09-05
    • Related Report
      2015 Annual Research Report
  • [Presentation] 初回再発悪性神経膠腫に対する摘出術後塩酸ニムスチンconvection enhanced delivery 投与とテモゾロミド内服―Phase I/II臨床試験―2014

    • Author(s)
      齋藤竜太、園田順彦、金森政之、隈部俊宏、冨永悌二
    • Organizer
      第32回日本脳腫瘍学会学術集会
    • Place of Presentation
      千葉、シェラトン・グランデ・トーキョウベイ・ホテル
    • Year and Date
      2014-11-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] MRIモニタリング下ニトロソウレア剤局所投薬による脳幹部再発神経膠腫新規治療法の開発2014

    • Author(s)
      齋藤竜太、園田順彦、金森政之、永松謙一、山下洋二、隈部俊宏、冨永悌二
    • Organizer
      日本脳神経外科学会 第73回学術総会
    • Place of Presentation
      東京、グランドプリンスホテル新高輪
    • Year and Date
      2014-10-11
    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] 薬液注入装置2016

    • Inventor(s)
      冨永悌二、齋藤竜太、佐藤綾耶、他8名
    • Industrial Property Rights Holder
      冨永悌二、齋藤竜太、佐藤綾耶、他8名
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-111559
    • Filing Date
      2016-06-03
    • Related Report
      2016 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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