| Project/Area Number |
15591355
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Jichi Medical School |
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Principal Investigator |
UNO Takeji Jichi Medical School, Dept of Surgery, Assistant, 医学部, 助手 (60185056)
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| Co-Investigator(Kenkyū-buntansha) |
KAWARASAKI Hideo Jichi Medical School, Dept of Surgery, Professor, 医学部, 教授 (60115475)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | DL-lactide / glycolide copolymer nanospheres / tacrolimus / sustained release drug delivery system / ポリ乳酸-グリコール酸共重合体 / ラット心移植 / 経口剤 / 局所免疫抑制 / ポリ乳酸グリコール酸共重合体 / 薬物担体 / ラット小腸移植 |
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| Research Abstract |
Objective : To develop DL-lactide/glycolide copolymer nanospheres (PLGA nanoshere) system to improve tacrolimus absorption and prolomg the physiological and immunosuppressive activity following oral administration.
Methods : We prepared PLGA nanosphere. LEW/SsN rats were given PLGA nanosphere at a dose of 4.8 mg/kg (n=5) tacrolimus contents, by a single oral administration to achieve sustained release over a long period. LEW/SsN rats were given PLGA nanosphere by a single oral administration at a dose of 4.8 mg/kg (n=5) tacrolimus contents to clarify the main site of PLGA nanosphere uptake in the organs. In the rat heart transplantation model, the recipients were given PLGA nanosphere at a dose of 4.8 mg/kg (n=5) tacrolimus contents by a single oral administration every other day for 2 weeks on the first day after operation compared with conventional formation every day for 2 weeks. Overall survival days of grafts were compared.
Results : The value of AUC and t_<1/2β>(half life of elimination phase) in the PLGA nanosphere was significantly higher (p<0.01) than in the conventional formulation. There were no significant differences in tacrolimus levels of organs between PLGA nanosphere and conventional formulation. However, there were no significant differences in graft survival between PLGA nanosphere, every other day and conventional formulation, every day.
Conclusion : PLGA nanosphere revealed a continuous flat concentration profile for 2 days after a single oral administration in the current study. This finding may suggest that it is possible to administer PLGA nanosphere one time per 2 days.
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