2002 Fiscal Year Final Research Report Summary
Active drug targeting to choroidal neovascularization by use of heat-sensitive liposomes
| Project/Area Number |
13557144
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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 | 展開研究 |
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| Research Field |
Ophthalmology
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| Research Institution | Kyoto University |
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Principal Investigator |
HONDA Yoshihiro Department of Ophthalmology and Visual Science, Kyoto Univ., Professor, 医学研究科, 教授 (90026930)
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| Co-Investigator(Kenkyū-buntansha) |
TABATA Yasuhiko Institute for Frontier Medical Sciences, Kyoto Univ., Professor, 再生医学研究所, 教授 (50211371)
NISHIMAKI Hirokazu Department of Ophthalmology and Visual Science, Kyoto Univ., Instructor, 医学研究科, 助手 (90303841)
KIRYU Junichi Department of Ophthalmology and Visual Science, Kyoto Univ., Lecturer, 医学研究科, 講師 (80281096)
HARA Kunihiko Topcon, Ltd., Chief Instructor, 医用機器事業部, 技術部・主席研究員
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| Project Period (FY) |
2001 – 2002
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| Keywords | heat-sensitive liposomes / retinochoroid / micro circulation / drug delivery system / choroidal neovascularization / interferon / fluorescein fundus angiography / laser |
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| Research Abstract |
Age-related macular degeneration (AMD) is a major cause of blindness in patients more than 50 years of age. Severe visual loss is often caused by angiogenesis originating from the choriocapillaris. Laser photocoagulation, vitreous surgery, radiation, and photodynamic therapy have been used to treat AMD. However, none of the current forms of therapy is effective against blindness from choroidal neovascularization (CNV). Active drug targeting mediated by heat-sensitive liposome of vascular endothelial cells in tumors is a new concept in cancer therapy. The objective of this study is to investigate the active drug targeting to CNV by means of heat-sensitive liposome. The targeting and inhibitory effects of interferon (IFN) combined with dextran on experimental CNV were studied in vivo. The effects of these substances were evaluated by fluorescein angiography and histology. To observe the accumulation of conjugate, the doses of IFNbeta in CNV tissues were measured by enzyme-linked immunosorbent assay. This conjugate prolonged the plasma half-life of IFNbeta and enabled IFNbeta to accumulate in the CNV in rabbits. The inhibition of immunoconjugates on the proliferation of human umbilical vein endothelial cells (HUVECs) was enhanced specifically by the mediatory effect of the mAb. Endothelial cells demonstrated strong immunoreactivity of integrin alphavbeta3 in the CNV. This study showed the choriocapillaris is divided into an independent functional unit. Human IFNbeta was successfully used to target CNV, an enhanced antiangiogenic effect was achieved by combining it with dextran, based on metal coordination. This targeted delivery of IFNbeta may have potential as a treatment modality for CNV.
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