Establishment of novel therapy for hepatitis C by double DDS drugs

• Project/Area Number: 22500410
• 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: Nihon University
• Principal Investigator: ISHIHARA Tsutomu 日本大学, 工学部, 准教授 (70349554)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ナノバイオロジー / ナノメディスン / DDS / ナノ粒子 / Ｃ型肝炎 / リバビリン / C型肝炎 / ポリ乳酸

Research Abstract

Novel drug carrier for ribavirin was developed for treatment of chronic hepatitis C. Polymeric nanoparticles encapsulating ribavirin were prepared fromarabinogalactan-poly(L-lysine) conjugates and poly(lactic acid). Ribavirin was specifically accumulated in the liver of mice and the amount of ribavirin was gradually decreased. Thus, it is expected that the nanoparticles are useful for treatment of chronic hepatitis C.

Research Products

• [Journal Article] Prostaglandin E1-encapsulated nanoparticles improve walking activity in an experimental rat model of intermittent claudication (2013)
  • Author(s): Ishihara T
  • Journal Title: Journal of Pharmacy and Pharmacology Volume: in press
  • Peer Reviewed
• [Journal Article] Fluorescent nucleosides with 'on-off' switching function, pH-responsive fluorescent uridine derivatives. (2012)
  • Author(s): Saito Y, Miyamoto S, Suzuki A, Matsumoto K, Ishihara T, Saito I.
  • Journal Title: Bioorg Med Chem Lett. Volume: 15 Pages: 2753-2756
  • Peer Reviewed
• [Journal Article] (N-isopropylacrylamide)-PLA and PLA blend nanoparticles for temperature-controllable drug release and intracellular uptake. (2012)
  • Author(s): Ayano E, Karaki M, Ishihara T, KanazawaH, Okano T. Poly
  • Journal Title: Colloids Surf B Biointerfaces. Volume: 99 Pages: 67-73
  • Peer Reviewed
• [Journal Article] Fluorescent nucleosides with 'on-off' switching function, pH-responsive fluorescent uridine derivatives (2012)
  • Author(s): Saito Y
  • Journal Title: Bioorg Med Chem Lett Volume: 15 Issue: 8 Pages: 2753-2756
  • DOI: 10.1016/j.bmcl.2012.02.092
  • Peer Reviewed
• [Journal Article] Nuclear localization and antisense effect of PNA internalized by ASGP-R-mediated endocytosis with protein/DNA conjugates. (2011)
  • Author(s): Ishihara T., Kano A., Obara K., Saito M., Chen X., Park T.G., Akaike T., Maruyama A.
  • Journal Title: J Control Release Volume: 155 Pages: 34-39
  • Peer Reviewed
• [Journal Article] Therapeutic effect of stealth-type polymeric nanoparticles with encapsulated betamethasone phosphate on experimental autoimmune uveoretinitis. (2011)
  • Author(s): Sakai T., Ishihara T., Higaki M.,Akiyama G., Tsuneoka H.
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: 52 Pages: 1516-1521
  • Peer Reviewed
• [Journal Article] Therapeutic effect of stealth-type polymeric nanoparticles with encapsulated betamethasone phosphate on experimental autoimmune uveoretinitis (2011)
  • Author(s): Sakai Tsutomu, et al
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 52 Issue: 3 Pages: 1516-1521
  • DOI: 10.1167/iovs.10-5676
  • Peer Reviewed
• [Journal Article] Nuclear localization and antisense effect of PNA internalized by ASGP-R-mediated endocytosis with protein/DNA conjugates (2011)
  • Author(s): Ishihara Tsutomu, et al
  • Journal Title: J Control Release Volume: 155 Issue: 1 Pages: 34-39
  • DOI: 10.1016/j.jconrel.2010.10.014
  • Peer Reviewed
• [Journal Article] Poly(N-isopropylacrylamide)-PLA and PLA blend nanoparticles for temperature-controllable drug release and intracellular uptake (2011)
  • Author(s): Eri ayano, Miyuki Karaki, Tsutomu Ishihara, Hideko Kanazawa, Teruo Okano
  • Journal Title: Colloids and Surfaces B : Biointerfaces Volume: (in press) Pages: 67-73
  • DOI: 10.1016/j.colsurfb.2011.10.003
  • Peer Reviewed
• [Journal Article] Stealth-nanoparticle strategy for enhancing the efficacy of steroids in mice with noise-induced hearing loss. (2010)
  • Author(s): Horie R., Sakamoto T., Nakagawa T., Ishihara T., Higaki M., Ito J.
  • Journal Title: Nanomedicine(Lond) Volume: 5 Pages: 1331-40
  • NAID: 120004184965
  • Peer Reviewed
• [Journal Article] Nano PGE1 promoted the recovery from spinal cord injury-induced motor dysfunction through its accumulation andsustained release. (2010)
  • Author(s): Takenaga M, Ishihara T, Ohta Y, Tokura Y, Hamaguchi A, Igarashi R, Mizushima T.
  • Journal Title: J Control. Release Volume: 148 Pages: 249-254
  • Peer Reviewed
• [Journal Article] Evasion of the accelerated blood clearance phenomenon by coating of nanoparticles with various hydrophilic polymers. (2010)
  • Author(s): Ishihara T., Maeda T., Sakamoto H., Takasaki N., Shigyo M., Ishida T., Kiwada H., Mizushima Y., Mizushima T.
  • Journal Title: Biomacromolecules Volume: 11
  • Peer Reviewed
• [Journal Article] Preparation and characterization of a nanoparticulate formulation composed of PEG-PLA and PLA as anti-inflammatoryagents. (2010)
  • Author(s): T. Ishihara, M. Takahashi, M. Higaki, Y. Mizushima, and T. Mizushima
  • Journal Title: Int.J. Pharm. Volume: 385 Pages: 170-175
  • Peer Reviewed
• [Journal Article] Therapeutic effect of lecithinized superoxide dismutase (PC-SOD) on bleomycin-induced pulmonary fibrosis. (2010)
  • Author(s): Tanaka KI., Ishihara T., Azuma A., Kudoh S., Ebina M., Nukiwa T., Sugiyama Y., Tasaka Y., Namba T., Ishihara T., Sato K., Mizushima Y., Mizushima T.
  • Journal Title: Am J Physiol Lung Cell Mol Physiol. Volume: 298
  • Peer Reviewed
• [Journal Article] Techniques for efficient entrapment of pharmaceuticals in biodegradable solid micro/nanoparticles. (2010)
  • Author(s): Ishihara T., Mizushima T.
  • Journal Title: Exp. Opinion on Drug Deliv. Volume: 7 Pages: 565-575
  • Peer Reviewed
• [Journal Article] Evasion of the accelerated blood clearance phenomenon by coating of nanoparticles with various hydrophilic polymers (2010)
  • Author(s): Ishihara Tsutomu, et al.
  • Journal Title: Biomacromolecules Volume: 11 Pages: 2700-2706
  • Peer Reviewed
• [Journal Article] Nano PGE1 promoted the recovery from spinal cord injury-induced motor dysfunction through its accumulation and sustained release. (2010)
  • Author(s): Takenaga Mitsuko, et al.
  • Journal Title: Journal of Controlled Release Volume: 148 Pages: 249-254
  • Peer Reviewed
• [Journal Article] Stealth-nanoparticle strategy for enhancing the efficacy of steroids in mice with noise-induced hearing loss (2010)
  • Author(s): Horie Rie, et al.
  • Journal Title: Nanomedicine(Lond) Volume: 5 Pages: 1331-1340
  • Peer Reviewed
• [Journal Article] Techniques for efficient entrapment of pharmaceuticals in biodegradable solid micro/nanoparticles (2010)
  • Author(s): Ishihara Tsutomu, et al.
  • Journal Title: Exp.Opinion on Drug Deliv Volume: 7 Pages: 565-575
  • Peer Reviewed
• [Journal Article] Preparation and characterization of a nanoparticulate formulation composed of PEG-PLA and PLA as anti-inflammatory agents (2010)
  • Author(s): Ishihara Tsutomu, et al.
  • Journal Title: Int.J.Pharm. Volume: 385 Pages: 170-175
  • Peer Reviewed
• [Journal Article] Prostaglandin E1-encapsulated nanoparticles improve walking activity in an experimental ratmodel of intermittent claudication
  • Author(s): Ishihara T, Takasaki N, Yamamoto S, Hayashi E, Takenaga M, Yamakawa N, Ishihara T, Mizushima T.
  • Journal Title: Journal of Pharmacy and Pharmacology. Volume: (in press)
  • Peer Reviewed
• [Presentation] 肝炎治療を目指したリバビリン封入ナノ粒子の開発 (2013)
  • Author(s): 石原務
  • Organizer: 第29回日本DDS学会
  • Place of Presentation: 京都
• [Presentation] リバビリンを封入した肝細胞特異的高分子ナノ粒子の開発 (2012)
  • Author(s): 石原務、平野展孝、斉藤義雄、春木満、宇野茂之、槇島誠、水島徹
  • Organizer: 第61回高分子学会討論会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-09-20
• [Presentation] 合成高分子を用いたナノ粒子型DDS製剤の開発 (2012)
  • Author(s): 石原務、平野展孝、斉藤義雄、春木満、宇野茂之、槇島誠
  • Organizer: 平成24年度化学系学協会東北大会
  • Place of Presentation: 秋田
  • Year and Date: 2012-09-16
• [Presentation] 合成高分子を用いたナノ粒子型DDS製剤の開発 (2012)
  • Author(s): 石原務
  • Organizer: 化学系学協会東北大会
  • Place of Presentation: 秋田
• [Presentation] DDS材料 (2010)
  • Author(s): 石原務
  • Organizer: 第27回医用高分子研究会講座
  • Place of Presentation: 東京
  • Year and Date: 2010-11-18
• [Presentation] PVP被覆ナノ粒子によるABC現象の回避 (2010)
  • Author(s): 石原務
  • Organizer: 第59回高分子学会年次大会
  • Place of Presentation: 横浜
  • Year and Date: 2010-05-27
• [Presentation] 合成高分子の医薬品への利用 (2010)
  • Author(s): 石原務
  • Organizer: 東北ポリマー懇話会
  • Place of Presentation: 郡山
• [Presentation] 生分解性高分子を用いたナノ粒子製剤の開発 (2010)
  • Author(s): 石原務
  • Organizer: 平成22年度化学系学協会東北大会
  • Place of Presentation: 盛岡
• [Presentation] 水島徹PVP被覆ナノ粒子によるABC現象の回避 (2010)
  • Author(s): 石原務、前田泰司、高崎奈央子
  • Organizer: 第59回高分子学会年次大会
  • Place of Presentation: 横浜
• [Remarks] 日本大学工学部生命応用科学科研究室紹介
  • URL: http://www.ce.nihon-u.ac.jp/seimei/labo.html
• [Remarks]
  • URL: http://www.ce.nihon-u.ac.jp/seimei/labo.html
• [Patent(Industrial Property Rights)] 薬物を封入した肝臓集積性ナノ粒子 (2011)
  • Inventor(s): 石原務、水島徹
  • Industrial Property Rights Holder: 石原務、水島徹
  • Industrial Property Number: 2011-192838
  • Filing Date: 2011-09-05