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Organization of nanoparticulate system by spherical crystallization for poorly absorbable drug

Research Project

Project/Area Number 13309013
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field 広領域
Research InstitutionGifu Pharmaceutical University

Principal Investigator

KAWASHIMA Yoshiaki  Gifu Pharmaceutical University Faculty of Pharmaceutical Science, Professor, 薬学部, 教授 (30082978)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Hiromitsu  Gifu Pharmaceutical University, Assistant Professor, PhD., 薬学部, 助手 (30275094)
TAKEUCHI Hirofumi  Gifu Pharmaceutical University, Associate Professor, PhD., 薬学部, 助教授 (50171616)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥37,960,000 (Direct Cost: ¥29,200,000、Indirect Cost: ¥8,760,000)
Fiscal Year 2003: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2002: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2001: ¥29,770,000 (Direct Cost: ¥22,900,000、Indirect Cost: ¥6,870,000)
KeywordsD,L-lactide / glycolide copolymer / spherical crystallization / nanosphere / pulmonary administration / intra-articular injection / surface modification / chitosan / plasmid DNA / 原子間力顕微鏡 / 粘膜付着性製剤 / 共焦点レーザー走査顕微鏡 / ポリスチレンナノスフェア / 関節注射用徐放性製剤 / 粉末吸入製剤 / エマルション溶媒核酸法 / プロピオン酸ベクロメタゾン / 経肺投与製剤用溶出試験法 / 難水溶性薬物 / 抗リュウマチ薬 / ナノ結晶
Research Abstract

The aim of this project is to design surface and size controlled nanoparticulate carrier for delivering poorly absorbable drug by the spherical crystallization process and to systemize the function of resulting nanoparticulate system.
1)Development of size and surface controlling method for carrier and evaluation of Physicochemical properties
Nanocrystals of beclomethasone dipropionate, a model of poorly water soluble drug, were prepared by the emulsion solvent diffusion (spherical crystallization) process, in which crystal growth and agglomeration occurred to produce composite system of crystals. Spherical and porous agglomerates were the most effectively delivered pulmonarily. Further their dissolution properties were much improved due to exceedingly large surface area and improved wettability of the composite of submicronsized crystals adsorbed with water soluble polymer.
2)Cell affinity of particle size and surface property-controlled nanoparticulate system
D, L-lactide/glycolide copolymer (PLGA) nanosphere loaded betamethasone sodium phosphate (BSP) was designed for controlled releasing delivery of the drug injected intra-articularly. In he antigen-induced arthritic rabbit, the joint swelling decreased significantly by administering BSP-loaded nanospheres during a 40-day period after intra-articular challenge, compared to the drug solution. The in vitro cytotoxicity of PLGA particulate system with L929 cell culture was determined by the particle size of system although the same material was used. The smaller PLGA nanospheres were more phagocytosed into the L929 cells. Particle size controlled PLGA nanosphere was more effectively uptaken into the cell. The surface modified nanosphere with chitosan showed higher cellular uptake and transfection efficiency than uncoated nanosphere due to enhanced cell affinity with chitosan modification.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (48 results)

All Other

All Publications (48 results)

  • [Publications] 竹内洋文, 山本浩充, 川島嘉明: "吸入剤の粒子設計"粉体工学会誌. 39. 22-27 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 山本浩充, 竹内洋文, 川島嘉明: "医薬品業界における湿式プロセス-サブミクロン化と晶析造粒-"粉体と工業. 33. 39-46 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 川島嘉明: "医薬品製剤開発のための粒子設計"ファルマシア. 37. 375-378 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 山本浩充, 竹内洋文, 川島嘉明: "粒子物性制御による微粒子ドラッグデリバリーシステムの機能設計"Drug Delivery System. 17. 321-329 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 堀沢栄次郎, 岩崎勝秀, 肘黒恒志, 竹井宏, 山本浩充, 竹内洋文, 川島嘉明: "局所投与を目指したPLGA微粒子キャリアーの細胞毒性と貪食作用に及ぼす粒子径の影響及び薬理効果に関する研究"薬剤学. 62. 189-202 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] E.Horisawa, K.Kubota, I.Tuboi, K.Sato, H.Yamamoto, H.Takeuchi, Y.Kawashima: "Size-Dependency of DL-Lactide/Glycolide Copolymer Particulates for Intra-Articular Delivery System on Phagocytosis in Rat Synovium"Pharm.Research. 19. 132-139 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] E.Horisuwa, T.Hirota, S.Kawazoe, J.Yamada, H.Yamamoto, H.Takeuchi, Y.Kawashima: "Prolonged Anti-Inflammatory Action of DL-Lactide/Glycolide Copolymer Nanospheres Containing Betamethasone Sodium Phosphate for an Intra-Articular Delivery in Antigen-Induced Arthritic Rabbit"Pharm.Research. 19. 403-410 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Kawashima, M.Imai, H.Takeuchi, H.Yamamoto, K.Kamiya: "Development of Agglomerated Crystals of Ascorbic Acid by the Spherical Crystallization Technique for Direct Tabletin"KONA. 20. 251-262 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Ikegami, Y.Kawashima, H.Takeuchi, H.Yamamoto, N.Isshiki, D.Momose, K.Ouchi: "Primary crystal growth during spherical agglomeration in liquid : design an ideal dry powder inhalation system"Powder Technol. 126. 266-274 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Ikegami, Y.Kawashima, H.Takeuchi, H.Yamamoto, K.Mimura, D.Momose, K.Ouchi: "A new spherically agglomerated drug composite system with lactose for dry powder inhalation"Adv.Powder Technol.. 14. 215-229 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Kawashima, M.Imai, H.Takeuchi, H.Yamamoto, K.Kamiya, T.Hino: "Improved flowability and compactibility of spherical agglomerated crystals of ascorbic acid for direct tableting designed by spherical crystallization process"Powder Technol.. 130. 283-289 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Ikegami, Y.Kawashima, H.Takeuchi, H.Yamamoto, K.Mimura, D.Momose, K.Ouchi: "A new agglomerated KSR-592 β-form crystal system for dry powder inhalation formulation to improve inhalation performance in vitro and in vivo"J.Controlled Release. 88. 23-33 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 堀沢栄次郎, 當別當健司, 小村昭夫, 竹井宏, 山本浩充, 竹内洋文, 川島嘉明: "関節炎治療を目的としたキトサンコーティングPLGAナノスフェアの研究:キトサンコーティングによるリウマチ患者由来・培養滑膜繊維芽細胞への結合促進効果"薬剤学. 63. 29-33 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 川島嘉明, 竹内洋文, 山本浩充: "微粒子工学大系 第II巻応用技術"フジ・テクノシステム. 7 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 川島嘉明, 竹内洋文, 山本浩充: "すぐに役立つ粒子設計・加工技術"じほう. 18 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Takeuchi, H.Yamamoto, Y.Kawashima: "Particulate Design for Inhalation Dosage Forms"Journal of the Society of Powder Technology Japan. 39. 22-27 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Yamamoto, H.Takeuchi, Y.Kawashima: "Wet Process in Pharmaceutical Industry -Submicronization and Crystaizing Agglomeration-"Powder Science and Engineering. 33. 39-46 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Kawashima: "Particle Design for Development of Pharmaceuticals"Farumashia. 37. 375-378 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] H.Yamamoto, H.Takeuchi, Y.Kawashima: "Functional design of microparticulate drug delivery systems by controlling particle physical properties"Drug Delivery System. 17. 321-329 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] E.Horisawa, K.Iwasaki, K.Hijikuro, H.Takei, H.Yamamoto, H.Takeuchi, Y.Kawashima: "Size-Dependency of Copoly (DL-Lactic/Glycolic Acid) Carrier Particles In Vitro Cytotoxicity, Phagocytosis and the Research of Local Therapeutic Action"YAKUZAIGAKU. 62. 189-202 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] E.Horisawa, K.Kubota, I.Tuboi, K.Sato, H.Yamamoto, H.Takeuchi, Y.Kawashima: "Size-Dependency of DL-Lactide/Glycolide Copolymer Particulates for Intra-Articular Delivery System on Phagocytosis in Rat Synovium"Pharm.Research. 19. 132-139 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] E.Horisawa, T.Hirota, S.Kawazoe, J.Yamada, H.Yamamoto, H.Takeuchi, Y.Kawashima: "Prolonged Anti-Inflammatory Action of DL-Lactide/Glycolide Copolymer Nanospheres Containing Betamethasone Sodium Phosphate for an Intra-Articular Delivery in Antigen-Induced Arthritic Rabbit"Pharm.Research. 19. 403-410 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Kawashima, M.Imai, H.Takeuchi, H.Yamamoto, K.Kamiya: "Development of Agglomerated Crystals of Ascorbic Acid by the Spherical Crystallization Technique for Direct Tableting"KONA. 20. 251-262 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Ikegami, Y.Kawashima, H.Takeuchi, H.Yamamoto, N.Isshiki, D.Momose, K.Ouchi: "Primary crystal growth during spherical agglomeration in liquid : design an ideal dry powder inhalation system"Powder Technol.. 126. 266-274 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Ikegami, Y.Kawashima, H.Takeuchi, H.Yamamoto, K.Mimura, D.Momose, K.Ouchi: "A new spherically agglomerated drug composite system with lactose for dry powder inhalation"Adv.Powder Technol.. 14. 215-229 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Kawashima, M.Imai, H.Takeuchi, H.Yamamoto, K.Kamiya, T.Hino: "Improved flowability and compactibility of spherical agglomerated crystals of ascorbic acid for direct tableting designed by spherical crystallization process"Powder Technol.. 130. 283-289 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Ikegami, Y.Kawashima, H.Takeuchi, H.Yamamoto, K.Mimura, D.Momose, K.Ouchi: "A new agglomerated KSR-592 β-form crystal system for dry powder inhalation formulation to improve inhalation performance in vitro and in vivo"J.Controlled Release. 88. 23-33 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] E.Horisawa, K.Tobetto, A.Komura, H.Takei, H.Yamamoto, H.Takeuchi, Y.Kawashima: "Development of copoly(DL-lactic/glycolic acid) nanospheres coated with chitosan to optimize intra-articular delivery system : Binding enhancement to synovial cells from patients with rheumatoid arthritis"Yakuzaigaku. 63. 29-33 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Kawashima, H.Takeuchi, H.Yamamoto: "Engineering System for Fine Particles Applied Technology II"Fuji Technosystem Co., LTD. (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Kawashima, H.Takeuchi, H.Yamamoto: "Particle Design and Pharmaceutical Technology"Jiho. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Ikegami, Y.Kawashima, H.Takeuchi, H.Yamamoto, N.Isshiki, D.Momose, K.Ouchi: "Primary crystal growth during spherical agglomeration in liquid : design an ideal dry powder inhalation system"Powder Technol. 126. 266-274 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Y.Kawashima, M.Imai, H.Takeuchi, H.Yamamoto, K.Kamiya: "Development of Agglomerated Crystals of Ascorbic Acid by the Spherical Crystal lization Technique for Direct Tableting"KONA. 20. 251-262 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Ikegami, Y.Kawashima, H.Takeuchi, H.Yamamoto, K.Mimura, D.Momose, K.Ouchi: "A new spherically agglomerated drug composite system with lactose for dry powder inhalation"Adv.Powder Technol.. 14. 215-229 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Y.Kawashima, M.Imai, H.Takeuchi, H.Yamamoto, K.Kamiya, T.Hino: "Improved flowability and compactibility of spherical agglomerated crystals of ascorbic acid for direct tableting designed by spherical crystallization process"Powder Technol.. 130. 283-289 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Ikegami, Y.Kawashima, H.Takeuchi, H.Yamamoto, K.Mimura, D.Momose, K.Ouchi: "A new agglomerated KSR-592 β-form crystal system for dry powder inhalation formulation to improve inhalation performance in vitro and in vivo"J.Controlled Release. 88. 23-33 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 堀沢栄次郎, 當別當健司, 小村昭夫, 竹井宏, 山本浩充, 竹内洋文, 川島嘉明: "関節炎治療を目的としたキトサンコーティングPLGAナノスフェアの研究:キトサンコーティングによるリウマチ患者由来・培養滑膜繊維芽細胞への結合促進効果"薬剤学. 63. 29-33 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 川島嘉明, 竹内洋文, 山本浩充: "すぐに役立つ粒子設計・加工技術"じほう. (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] E.Horisawa, K.Kubota, I.Tuboi, K.Sato, H.Yamamoto, H.Takeuchi, Y.Kawashima: "Size-Dependency of DL-Lactide/Glycolide Copolymer Particulates for Intra-Articular Delivery System on Phagocytosis in Rat Synovium"Pharm.Research. 19. 132-139 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] E.Horisawa, T.Hirota, S.Kawazoe, J.Yamada, H.Yamamoto, H.Takeuchi, Y.Kawashima: "Prolonged Anti-Inflammatory Action of DL-Lactide/Glycolide Copolymer Nanospheres Containing Betamethasone Sodium Phosphate for an Intra-Articular Delivery in Antigen-Induced Arthritic Rabbit"Pharm.Research. 19. 403-410 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 山本浩充, 竹内洋文, 川島嘉明: "粒子物性制御による微粒子ドラッグデリバリーシステムの機能設計"Drug Delivery System. 17. 231-239 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 堀沢栄次郎, 岩崎勝秀, 肘黒恒志, 竹井弘, 山本浩充, 竹内洋文, 川島嘉明: "局所投与を目的としたPLGA微粒子キャリアーの細胞毒性と貪食作用に及ぼす粒子径の影響及び薬理効果に関する研究"薬剤学. 62. 189-202 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 川島嘉明, 竹内洋文, 山本浩充: "微粒子工学大系 第II巻応用技術"フジ・テクノシステム. 7 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 川島嘉明: "医薬品製剤開発のための粒子設計"ファルマシア. 37. 375-378 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] E.Horisawa, Y.Kawashima, H.Takeuchi, H.Yamamoto, et al.: "Size-Dependency of DL-Lactide/Glycolide Copolymer Particulates for Intra-Articular Delivery System on Phagocytosis in Rat Synovium"Pharmaceutical Research. 19. 132-139 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] E.Horisawa, Y.Kawashima, H.Takeuchi, H.Yamamoto, et al.: "Prolonged Anti-Inflammatory Action of DL-Lactide/Glycolide Copolymer Nanospheres Containing Betamethasone Sodium Phosphate for an Intra-Articular Delivery System in Antigen-Induced Arthritic Rabbit"Pharmaceutical Research. 19. 403 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 山本浩充, 竹内洋文, 川島嘉明: "医薬品業界における湿式プロセス -サブミクロン化と晶析造粒-"粉体と工業. 33. 39-46 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 竹内洋文, 山本浩充, 川島嘉明: "吸入剤の粒子設計"粉体工学会誌. 39. 22-27 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 川島嘉明, 竹内洋文, 山本浩充: "微粒子工学大系"フジテクノシステム. 7 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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