| Project/Area Number |
13309013
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
広領域
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| Research Institution | Gifu Pharmaceutical University |
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Principal Investigator |
KAWASHIMA Yoshiaki Gifu Pharmaceutical University Faculty of Pharmaceutical Science, Professor, 薬学部, 教授 (30082978)
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| 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)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| 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)
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| Keywords | D,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 |
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| 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.
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