• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of bioactive substance delivery system to the vitreous and retina with biodegradable hydrogels

Research Project

Project/Area Number 12557148
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Ophthalmology
Research InstitutionNagoya City University

Principal Investigator

OGURA Yuichiro  Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院・医学研究科, 教授 (70191963)

Co-Investigator(Kenkyū-buntansha) KUWANO Mitsuaki  Santen Pharmaceutical. Co., Ophthalmic Research Division, General Manager, 眼科動態研究グループ, グループ長
TABATA Yasuhiko  Kyoto University, Institute for Frontier Medical Sciences, Professor, 再生医科学研究所, 教授 (50211371)
KIMURA Hideya  Nagoya City University, Graduate School of Medecal Sciences, Assosiate Professor, 大学院・医学研究科, 助教授 (50252440)
尾関 年則  名古屋市立大学, 医学部, 講師 (60254299)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2002: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2000: ¥4,800,000 (Direct Cost: ¥4,800,000)
Keywordsbiodegradable polymes / hydrogels / bioactive proteins / interferon / choroidal neovascularization / 血管新生 / 硝子体 / 強膜 / 生体分解 / 網膜硝子体 / 生理活性物質 / 高分子
Research Abstract

Targeting and inhibitory effects of IFN combined with dextran on experimental choroidal neovascularization (CNM) were studied. Interferon (IFN) β was conjugated to dextran, which has metal-chelating, diethylenetriaminepentaacetic acid (DTPA) residues. Based on metal coordination, conjugation of IFNβ with DTPA-dextran resulted from simply mixing both substances in an aqueous solution containing Zn^<2+>. The effects of IFNβ on the proliferation human umbilical vein endothelial cells (HUVECs) and bovine retinal pigment epithelial cells (BRPECs) were evaleated. To evaluate the activity loss of IFNβ by conjugation, the effect of the conjugate on HUVECs was compared with that of IFNβ. Experimental CNV was induced by subretinal injection of gelatin microspheres containing basic fibroblast growth factor in rabbits. The rabbits with CNV were intravenously treated twice weekly with 7.5 million international units (MIU)/kg per day free IFNβ (for 4 weeks), with IFNβ-DTPA-dextran conjugate containing 7.5 (for 2 weeks) or 0.75 (for 4 weeks) MIU/kg per day IFNβ, or with saline. The effects of these substances were evaluated by fluorescein angiography and histology. To observe the accumulation of conjugate, the doses of IFNβ in CNV tissues were measured by enzyme-linked immunosorbent assay. IFNβ inhibited the growth of HUVECs and enhanced the proliferation of BRPECs. The conjugate seemed to preserve approximately 44% of IFNβ activity. Although both doses of IFNβ-DTPA-dextran inhibited progression of CNV in rabbits, longer term administration of a lower dose of IFNβ-DTPA-dextran had a sustained inhibitory effect on progression of CNV (P<0.05). Histologic studies revealed the inhibitory effect of IFNβ-DTPA-dextran on progression of CNV. This conjugate prolonged the plasma half-life of IFNβ and enabled IFNβ to accumulate the CNV in rabbits.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Yasukawa T: "Active drug targeting with immunoconjugates to choroidal neovascularization"Cur Eye Res. 21. 952-961 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakurai E: "Scleral plug of biodegradable polymers containing ganciclovir for experimental cytomegalovirus retinitis"Invest Ophthalmol Vis Sci. 42. 2043-2048 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kamizuru H: "Monoclonal antibody-mediated drug targeting to choroidal neovascularization in the rat"Invest Ophthalmol Vis Sci. 42. 2664-2672 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yasukawa T: "Targeting of interferon to choroidal neovascularization by use of dextran and metal coordination"Invest Ophthalmol Vis Sci. 43. 842-848 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okabe J: "Biodegradable intrascleral implant for sustained delivery of betamethasone phosphate"Invest Ophthalmol Vis Sci. 44. 740-744 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yasukawa,T., et al.: "Active drug targeting with immunoconjugates to choroidal neovascularization"Cur Eye Res. 21. 952-961 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakurai,E., et al.: "Scleral plug of biodegradable polymers containing ganciclovir for experimental cytomegalovirus retinitis"Invent Ophthalmol Vis Sci. 42. 2043-2048 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kamizuru H., et al.: "Monoclonal antibody-mediated drug targeting to choroidal neovascularization in the rat"Invest Ophthalmol Vis Sci. 42. 2664-2672 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yasukawa T., et al.: "Targeting of interferon to choroidal neovascularization by use of dextran and metal coordination"Invest Ophthalmol Vis Sci. 43. 842-848 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okabe J., et al.: "Biodegradable intrascleral implant for sustained delivery of betamethasone phosphate"Invest Ophthalmol Vis Sci. 44. 740-744 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yasukawa T: "Targeting of interferon to choroidal neovascularization by use of dextran and metal coordination"Investigative Ophthalmology and Visual Science. 43. 842-847 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ogura, Y.: "Drug delivery to the posterior segments of the eye"Advanced Drug Delivery Rev. 52. 1-3 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yasukawa, T.: "Biodegradable scieral plugs for vitreoretinal drug delivery"Advanced Drug Delivery Rev. 52. 25-26 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yang,C.F.: "Experimental corneal neovascularization by basic fibroblast growth factor incorporated into gelatin hydrogel"Ophthalmic Res. 32. 19-24 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamamoto,M.: "Bone regeneration by transforming growth factor betal released from a biodegradable hydrogel"J Control Release. 64. 133-142 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tabata,Y.: "Controlled release of vascular endothelial growth factor by use of collagen hydrogels"J Biomater Sci Polym Ed. 11. 915-930 (2000)

    • Related Report
      2000 Annual Research Report

URL: 

Published: 2000-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi