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Development of peptide-delivery system using nanogel carrier for the control release of the peptide as the inhibitor of bone resorption toward clinical applications

Research Project

Project/Area Number 19390472
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

AOKI Kazuhiro  Tokyo Medical and Dental University, 大学院・医歯学総合研究科, 助教 (40272603)

Co-Investigator(Kenkyū-buntansha) MORIMOTO Nobuyuki  東京医科歯科大学, 生体材料工学研究所, 助教 (00313263)
Co-Investigator(Renkei-kenkyūsha) ROLAND Baron  Harvard, 大歯学部, 教授
Research Collaborator OHYA Keiichi  東京医科歯科大学, 大学院・医歯学総合研究科, 教授
AKIYOSHI Kazunari  東京医科歯科大学, 生体材料工学研究所, 教授
SHIMOKAWA Hitoyata  東京医科歯科大学, 大学院・医歯学総合研究科, 前准教授
陽子 Yoko  東京医科歯科大学, 生体材料工学研究所, 修士課程修了
SHIMODA Asako  東京医科歯科大学, 生体材料工学研究所, 博士課程在学中
SAITO Hiroaki  東京医科歯科大学, 大学院・医歯学総合研究科, 非常勤講師
MD ANOWER Hussain Mian  東京医科歯科大学, 大学院・医歯学総合研究科, 博士課程修了
NIROSHANI Soysa  東京医科歯科大学, 大学院・医歯学総合研究科, 博士研究員
NEIL Alles  東京医科歯科大学, 大学院・医歯学総合研究科, 博士課程在学中
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2008: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2007: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywords骨吸収抑制ペプチド / ナノゲル / 薬物送達システム / 徐放ゲル / 低カルシウム食飼育 / マウス / 破骨細胞 / W9ペプチド / DDS / 骨吸収抑制 / 骨形態計測 / 低カルシウム食 / コントロールリリース / WP9QY(W9)ペプチド / 徐放性担体
Research Abstract

ポストゲノム時代において、タンパク質の結晶構造解析情報をもとにペプチド薬を設計する機会が増えてきている。ところが、ペプチド自体、易分解性であり、安定性に欠け、実際の臨床応用に際して障害が多い。我々はペプチド薬の臨床応用のために、骨破壊を抑制するW9ペプチドを用い、ペプチド薬をコントロールリリースできる担体を検討した。本研究により、ペプチドの担体として、コレステロールとプルランとの合成体であるCHPナノゲルがペプチドの担体として使用できる性質を持ち合わせていることを明らかにできた。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (34 results)

All 2009 2008 2007 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (14 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Polysaccharide nanogel delivery of a TNF-alpha and RANKL antagonist peptide allows systemic prevention of bone loss2009

    • Author(s)
      Alles, N., Soysa, N.S., Hussain, M.D., Tomomatsu, N., Saito, H., Baron, R., Morimoto, N., Aoki, K., Akiyoshi, K., Ohya, K
    • Journal Title

      Eur J Pharm Sci 37(2)

      Pages: 83-88

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of the classical NF-kappaB pathway prevents osteoclast bone-resorbing activity2009

    • Author(s)
      Soysa, N. S., Alles, N., Shimokawa, H., Jimi, E., Aoki, K., Ohya, K
    • Journal Title

      J Bone Miner Metab 27(2)

      Pages: 131-9

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bovine dentine organic matrix down-regulates osteoclast activity2009

    • Author(s)
      Sriarj, W., Aoki, K., Ohya, K., Takagi, Y., Shimokawa, H
    • Journal Title

      J Bone Miner Metab 27(3)

      Pages: 315-23

    • NAID

      10025337365

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of the classical NF-kB pathway preventsOS teoclast bone-resorbing act ivi ty.2009

    • Author(s)
      N Soysa, et al. (K. Aoki ; Corresponding author)
    • Journal Title

      J Bone Miner Metab Vol. 27

      Pages: 131-139

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Polysaccharide nanogel del ivery of a TNF-α and RANKL antagonis tpeptide allows systemic prevention of bone loss2009

    • Author(s)
      Neil Alles, et al. (K. Aoki ; Corresponding author)
    • Journal Title

      European Journal of Pharmaceutical Sciences Vol. 37

      Pages: 83-88

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cathepsin K-Dependent Toll-Like Receptor 9 Signaling Revealed in Experimental Arthritis2008

    • Author(s)
      Asagiri M, Hirai T, Kunigami T, Kamano S, Gober H-J, Okamoto K, Nishikawa K, Latz E, Golenbock D.T, Aoki K, Ohya K, Imai Y, Morishita Y, Miyazono K, Kato S, Saftig P, Takayanagi H
    • Journal Title

      Science 1319

      Pages: 624-627

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lipopolysaccharide-induced bone resorption is increased in TNF type 2 receptor-deficient mice in vivo2008

    • Author(s)
      Mian MD, Saito H, Alles N, Shimokawa H, Aoki K, Ohya K
    • Journal Title

      J Bone Miner Metab 26

      Pages: 469-477

    • NAID

      10024459458

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cathepsin K-Dependent Toll-Like Receptor 9 Signaling Revealedin Experimental Arthritis.2008

    • Author(s)
      Asagiri M, et al. 17人中10番目
    • Journal Title

      Science Vol. 319

      Pages: 624-627

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lipopolysaccharide-induced bone resorption is increased in TNF type 2 receptor-deficient mice in vivo.2008

    • Author(s)
      Mian MD, et al. (K. Aoki : Corresponding author)
    • Journal Title

      J Bone Miner Metab Vol. 26

      Pages: 469-477

    • NAID

      10024459458

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A tumor necrosis factor receptor loop peptide mimic inhibits bone destruction to the same extent as anti-tumor necrosis factor monoclonal antibody in murine collagen-induced arthritis2007

    • Author(s)
      Saito H, Kojima T, Takahashi M, Horne WC, Baron R, Amagasa T, Ohya K, Aoki K
    • Journal Title

      Arthritis Rheum 56

      Pages: 1164-1174

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Schlessinger J.Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2(-/-) mice2007

    • Author(s)
      Gil-Henn H, Destaing O, Sims NA, Aoki K, Alles N, Neff L, Sanjay A, Bruzzaniti A, De Camilli P, Baron R
    • Journal Title

      J Cell Biol 178

      Pages: 1053-1064

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] NF inhibitor dehydroxymethylepoxyquinomicin(DHMEQ)suppresses osteoclastogenesis and expression of NFATc1 in mouse arthritis without affecting expression of RANKL, OPG or M-CSF2007

    • Author(s)
      Kubota T, Hoshino M, Aoki K, Ohya K, Komano Y, Nanki T, Miyasaka N, Umezawa K
    • Journal Title

      Arthritis Res Ther 9

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2(-/-)mice.2007

    • Author(s)
      Gil-Henn H, Destaing O, Sims NA, Aoki K, Alles N, Neff L, Saniay A, Bruzzaniti A, De Camilli P, Baron R, Schlessinger J.
    • Journal Title

      Journal of cell biology 178

      Pages: 1053-1064

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NF-κβ inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) suppressesosteoclastogenesis and expression of NFATc1 in mouse arthritiswithout affecting expression of RANKL, OPG or M-CSF.2007

    • Author(s)
      Kubota T, Hoshino M. Aoki K, Ohya K, Komano Y, Nanki T, Miyasaka N, Umezawa K.
    • Journal Title

      Arthritis research & therapy 9

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A tumor necrosis factor receptor loop peptide mimic inhibits bone destruction to the same extent as anti-tumor necrosis factor monoclonal antibody in murine collagen-induced arthritis.2007

    • Author(s)
      Saito H, Koiima T, Takahashi M, Horne WC, Baron R, Amagasa T, Ohya K, Aoki K.
    • Journal Title

      Arthritis and rheumatism 56

      Pages: 1164-1174

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] LPS-Induced Inhibition of Osteogenesis is TNF-α-Dependent in a Murine Tooth Extraction Model

    • Author(s)
      Tomomatsu, N., Aoki, K., Alles, N., Soysa, N.S., Hussain, A., Nakachi, H., Kita, S., Shimokawa, H., Ohya, K., Amagasa, T
    • Journal Title

      J Bone Miner Res online publication

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Presentation] Drug development for inflammatory bone disease2008

    • Author(s)
      Aoki K, Ohya K
    • Organizer
      The 81thAnnual Meeting of the Japanese Pharmacological Society(第81回日本薬理学会年会)
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report
  • [Presentation] Nanogel Cross-linking Hydrogel as a Drug Delivery System for Tumor Necrosis Factor-α Antagonist2008

    • Author(s)
      Alles N, Soysa N, Mian MD, Tomomatsu N, Morimoto N, Hasegawa U, Sawada S, Tada Y, Akiyoshi K, Ohya K, Aoki K
    • Organizer
      30th ASBMR Annual Meeting
    • Place of Presentation
      Montrea
    • Related Report
      2008 Final Research Report
  • [Presentation] Nanogel cross-linking hydrogel as a drug delivery system for the peptide type of drugs2008

    • Author(s)
      Alles N, Soysa N, 青木和広, 大谷啓一
    • Organizer
      第50回歯科基礎医学会学術大会・総会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] 破骨細胞機能抑制ペプチドによる臨床応用の可能性2008

    • Author(s)
      青木和広,Alles N, Soysa N, 自見英治郎, 下川仁彌太, 大谷啓一
    • Organizer
      第50回歯科基礎医学会学術大会・総会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] ライオン学術賞受賞講演「ペプチド創薬の炎症性骨吸収疾患に対する応用と将来への展望」2008

    • Author(s)
      青木和広
    • Organizer
      第50回歯科基礎医学会学術大会・総会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] Nanogel Cross-1inking Hydrogel as a Drug Delivery System forTumor Necrosis Factor-alpha Antagonist.2008

    • Author(s)
      Neil Alles, et al.
    • Organizer
      30'" ASBMR Annual Meeting
    • Place of Presentation
      Montreal
    • Related Report
      2008 Annual Research Report
  • [Presentation] Nanogel cross-1inking hydrogel as a drug delivery system forthe peptide type of drugs.2008

    • Author(s)
      Neil Alles, et al.
    • Organizer
      第50回歯科基礎医学会学術大会・総会
    • Place of Presentation
      東京
    • Related Report
      2008 Annual Research Report
  • [Presentation] Drug development for inflammatory bone disease.2008

    • Author(s)
      Aoki K, Ohya K.
    • Organizer
      The 81th Annual Meeting of the Japanese Pharmacological Society(第81回日本薬理学会年会)
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] Application of CHP Nanogel as a drug delivery system for tumor necrosis factor-α peptide antagonist in murine bone resorption model2007

    • Author(s)
      Alles N, Soysa N, Mian H, 青木和広、大谷啓一
    • Organizer
      第27回日本骨形態計測学会The 27th Annual Meeting of the Japanese Society for Bone Morphometry
    • Place of Presentation
      長崎
    • Related Report
      2008 Final Research Report
  • [Presentation] Use of Nanogels as a Drug Delivery System for Tumor Necrosis Factor-α Antagonist in Murine Bone Resorption Model2007

    • Author(s)
      Alles N, Mian H, Soysa N, Saito H, Aoki K, Akiyoshi K, Ohya K
    • Organizer
      ASBMR 29th Annual Meeting
    • Place of Presentation
      Honolulu
    • Related Report
      2008 Final Research Report
  • [Presentation] TNFアンタゴニストによる骨吸収阻害2007

    • Author(s)
      青木和広、齋藤広章, Baron R, 大谷啓一
    • Organizer
      第35回薬物活性シンポジウム
    • Place of Presentation
      広島
    • Related Report
      2008 Final Research Report
  • [Presentation] Application of CHP Nanogel as a drug delivery system for tumornecrosis factor-α peptide antagonist in murine bone resorptionmodel.2007

    • Author(s)
      Alles N, Soysa N, Mian H, 青木和広、大谷啓一
    • Organizer
      第27回日本骨形態計測学会 The 27th Annual Meeting of the Japanese Society for Bone Morphometry.
    • Place of Presentation
      長崎
    • Related Report
      2007 Annual Research Report
  • [Presentation] Use of Nanogels as a Drug Delivery System for Tumor Necrosis Factor-α Antagonist in Murine Bone Resorption Model.2007

    • Author(s)
      Alles N, Mian H, Soysa N, Saito H, Aoki K, Akiyoshi K, Ohya K.
    • Organizer
      ASBMR 29th Annual Meeting.
    • Place of Presentation
      Hono lulu
    • Related Report
      2007 Annual Research Report
  • [Presentation] TNFアンタゴニストによる骨吸収阻害.2007

    • Author(s)
      青木和広、齋藤広章, Baron R, 大谷啓一
    • Organizer
      第35回薬物活性シンポジウム.
    • Place of Presentation
      広島
    • Related Report
      2007 Annual Research Report
  • [Book] 腫瘍壊死因子中和療法の新しい展開-WP9QYペプチドによる治療の可能性-2007

    • Author(s)
      青木和広, 大谷啓一
    • Publisher
      日本歯科評論(The Nippon Dental Review)
    • Related Report
      2008 Final Research Report
  • [Book] 腫瘍壊死因子中和療法の新しい展開-WP9QYペプチドによる治療の可能性-.日本歯科評論(The Nippon Dental Review)Vol.67(7)2007

    • Author(s)
      青木和広, 大谷啓一
    • Publisher
      株式会社ヒョーロンパブリッシャーズ
    • Related Report
      2007 Annual Research Report
  • [Remarks] この研究成果を含めたペプチド薬の一連の研究が評価され、第50回歯科基礎医学会学術大会において第8回ライオン学術賞を受賞した。

    • Related Report
      2008 Final Research Report
  • [Remarks]

    • URL

      http://www.tmd.ac.jp/grad/hpha/2008nen.htm

    • Related Report
      2008 Annual Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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