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Investigation into unraveling the mechanism of drug delivery system to the inner ear

Research Project

Project/Area Number 16K11180
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Otorhinolaryngology
Research InstitutionKyoto University

Principal Investigator

Kita Tomoko  京都大学, 医学研究科, 研究員 (20362519)

Co-Investigator(Kenkyū-buntansha) 中川 隆之  京都大学, 医学研究科, 講師 (50335270)
山田 勇磨  北海道大学, 薬学研究院, 准教授 (60451431)
山口 太郎  摂南大学, 薬学部, 助教 (30710701)
北尻 真一郎  信州大学, 学術研究院医学系(医学部附属病院), 講師 (00532970)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords内耳蝸牛 / 薬物送達 / 血液内耳関門 / 内耳 / ドラッグデリバリー / ナノキャリア
Outline of Final Research Achievements

The final aim of this study was to achieve the effective drug delivery systems to the inner ear. First, we tried to establish the culture system of blood-labyrinth barrier but unfortunately failed. And second, to clarify the contribution of each drug transporter expressed in this inner ear barrier, we have established the preparation protocols of cDNA library from samples obtained by laser capture micro dissection. Third, using several model drugs for each drug transporter and their inhibitors, it was shown that several tissue type specific transporters are localized in the inner ear barrier, but there was no significant change in the distribution of each model drug.

Academic Significance and Societal Importance of the Research Achievements

内耳を標的とした創薬開発において、薬物の内耳への効率的な移行性は効果につながることから非常に重要である。本研究での成果はまだ序章にすぎないが、幾つかの改善点ならびに注意点が明らかになったことは、意義が高い。

Report

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

    (14 results)

All 2019 2018 2017 2016

All Journal Article (14 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 14 results,  Open Access: 8 results,  Acknowledgement Compliant: 2 results)

  • [Journal Article] Disruption of Gap Junction-Mediated Intercellular Communication in the Spiral Ligament Causes Hearing and Outer Hair Cell Loss in the Cochlea of Mice2019

    • Author(s)
      Norito Nishiyama, Taro Yamaguchi, Masanori Yoneyama, Yusuke Onaka, Kiyokazu Ogita
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 1 Pages: 73-80

    • DOI

      10.1248/bpb.b18-00559

    • NAID

      130007542229

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-01-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The use of a microfluidic device to encapsulate a poorly water-soluble drug CoQ10 in lipid nanoparticles and an attempt to regulate intracellular trafficking to reach mitochondria2019

    • Author(s)
      Hibino Mitsue、Yamada Yuma、Fujishita Naoki、Sato Yusuke、Maeki Masatoshi、Tokeshi Manabu、Harashima Hideyoshi
    • Journal Title

      Journal of Pharmaceutical Sciences

      Volume: 印刷中 Issue: 8 Pages: 2668-2676

    • DOI

      10.1016/j.xphs.2019.04.001

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Insulin-like growth factor 1 promotes cochlear synapse regeneration after excitotoxic trauma in vitro.2019

    • Author(s)
      Yamahara K, Asaka N, Kita T, Kishimoto I, Matsunaga M, Yamamoto N, Omori K, Nakagawa T.
    • Journal Title

      Hear Res

      Volume: 374 Pages: 5-1

    • DOI

      10.1016/j.heares.2019.01.008

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hearing preservation at low frequencies by insulin-like growth factor 1 in a guinea pig model of cochlear implantation.2018

    • Author(s)
      Yamahara K, Nishimura K, Ogita H, Ito J, Nakagawa T, Furuta I, Kita T, Omori K, Yamamoto N.
    • Journal Title

      Hear Res.

      Volume: 368 Pages: 92-108

    • DOI

      10.1016/j.heares.2018.07.004

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FGFR1-mediated protocadherin-15 loading mediates cargo specificity during intraflagellar transport in inner ear hair-cell kinocilia2018

    • Author(s)
      Honda Akira、Kita Tomoko、Seshadri Shri Vidhya、Misaki Kazuyo、Ahmed Zamal、Ladbury John E.、Richardson Guy P.、Yonemura Shigenobu、Ladher Raj K.
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 115 Issue: 33 Pages: 8388-8393

    • DOI

      10.1073/pnas.1719861115

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In Vivo Transgene Expression in the Pancreas by the Intraductal Injection of Naked Plasmid DNA.2018

    • Author(s)
      Yamada Y, Tabata M, Abe J, Nomura M, Harashima H.
    • Journal Title

      J Pharm Sci.

      Volume: 107 Issue: 2 Pages: 647-653

    • DOI

      10.1016/j.xphs.2017.09.021

    • NAID

      120006558999

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Netrin 1 mediates protective effects exerted by insulin-like growth factor 1 on cochlear hair cells.2017

    • Author(s)
      Yamahara K, Nakagawa T, Ito J, Kinoshita K, Omori K, Yamamoto N.
    • Journal Title

      Neuropharmacology.

      Volume: 119 Pages: 26-39

    • DOI

      10.1016/j.neuropharm.2017.03.032

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Microarray analyses of otospheres derived from the cochlea in the inner ear identify putative transcription factors that regulate the characteristics of otospheres.2017

    • Author(s)
      Iki T, Tanaka M, Kitajiri SI, Kita T, Kawasaki Y, Mizukoshi A, Fujibuchi W, Nakagawa T, Nakahata T, Ito J, Omori K, Saito MK.
    • Journal Title

      PLoS One.

      Volume: 12 Issue: 6 Pages: e0179901-e0179901

    • DOI

      10.1371/journal.pone.0179901

    • NAID

      120006782202

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Validation of the use of an artificial mitochondrial reporter DNA vector containing a Cytomegalovirus promoter for mitochondrial transgene expression.2017

    • Author(s)
      Yamada Y, Ishikawa T, Harashima H.
    • Journal Title

      Biomaterials.

      Volume: 136 Pages: 56-66

    • DOI

      10.1016/j.biomaterials.2017.05.016

    • NAID

      120006716305

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Innovative technologies in Nanomedicines: from passive targeting to active targeting/from controlled pharmacokinetics to controlled intracellular pharmacokinetics.2017

    • Author(s)
      Sato Y, Sakurai Y, Kajimoto K, Nakamura T, Yamada Y, Akita H, Harashima H.
    • Journal Title

      Macromolecular Bioscience

      Volume: 17 Issue: 1 Pages: 1-16

    • DOI

      10.1002/mabi.201600179

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Quantitative Analysis of Aquaporin Expression Levels during the Development and Maturation of the Inner Ear2017

    • Author(s)
      Miyoshi, T. Yamaguchi, T. Ogita, K. Tanaka, Y. Ishibashi, K. I. Ito, H. Kobayashi, T. Nakagawa, T. Ito, J. Omori, K. Yamamoto, N.
    • Journal Title

      J Assoc Res Otolaryngol

      Volume: 18 Issue: 2 Pages: 247-261

    • DOI

      10.1007/s10162-016-0607-3

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Calpain inhibitor alleviates permanent hearing loss induced by intense noise by preventing disruption of gap junction-mediated intercellular communication in the cochlear spiral ligament.2017

    • Author(s)
      Yamaguchi T, Yoneyama M, Ogita K
    • Journal Title

      Eur J Pharmacol.

      Volume: 2999 Pages: 30228-5

    • DOI

      10.1016/j.ejphar.2017.03.058

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Development of a multifunctional envelope-type nano device and its application to nanomedicine.2016

    • Author(s)
      Sato Y, Nakamura T, Yamada Y, Harashima H.
    • Journal Title

      J Control Release

      Volume: 244 Pages: 194-204

    • DOI

      10.1016/j.jconrel.2016.06.042

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Tricellular tight junctions in the inner ear2016

    • Author(s)
      Shin-ichiro Kitajiri, Tatsuya Katsuno
    • Journal Title

      BioMed Research International

      Volume: - Pages: 6137541-6137541

    • DOI

      10.1155/2016/6137541

    • NAID

      120005770756

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access

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

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