| Project/Area Number |
07457411
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
OGURA Yuichiro Graduete School of Medicine, Kyoto University Associate Professor, 医学研究科, 助教授 (70191963)
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| Co-Investigator(Kenkyū-buntansha) |
OKAMOTO Naoyuki Graduate School of Medicine, Kyoto University Instructor, 医学研究科, 助手 (70263069)
KITA Mihori Graduate School of Medicine, Kyoto University Instructor, 医学研究科, 助手 (00252453)
TANIHARA Hidenobu Graduate School of Medicine, Kyoto University Lecturer, 医学研究科, 講師 (60217148)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥7,700,000 (Direct Cost: ¥7,700,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥6,900,000 (Direct Cost: ¥6,900,000)
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| Keywords | poly-lactide / poly-glycolidt / Biodegradable polymer / Vitreous body / retina / ganciclovir / fluconazole / Steroid / 強膜プラグ / 薬物放出制御システム / 抗真菌剤 / 副腎皮質ホルモン / 生体分離性高分子 / ガンサイクロヴィル |
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| Research Abstract |
We have developed a new intravitreal drug delivery system using biodegradable polymers. Scleral implants loaded with ganciclovir were prepared with poly-lactic acid or poly-glycolic acid. The scleral implants released ganciclovir for 3 weeks to 6 months in vitro. The release rate of ganciclovir was controllable by changing the molecular weight, the monomer conposition of the copolymers, and the rate of the drug incorporated into the polymers. The ganciclovir concentration in the range of ED90 for human cytomegalovirus retinitis was maintained in the vitreous of rabbits for 12 weeks by the implant loaded with 25% ganciclovir. The implant showed good biocompatibility and no toxicity electrophisiologically and histrogically. The implant loaded with fluconazole, antifungal agent, and betamethasone phosphate, antiinflammatory agent, released the drugs for several weeks both in vitro and in vivo. These results suggest that the scleral implants of biodegradable polymers are feasible for intravitreal drug delivery system.
Biodegradable polymer microspheres with a fluorescent dye as a drug marker was administered into the subretinal space via transvitreal approach in the rabbits in vivo. Microspheres were phagocytosed by retinal pigment epithelium cells and the dye was released intracellularly. Subretinal neovascularization could be induced by microspheres incorporated with basic fibroblast growth factor, an angiogenic factor, administered into the subretinal space. This drug delivery system may enable the functions of retinal pigment epithelium cells to be modified pharmacologically.
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