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Active drug targeting to choroidal neovascularization by use of heat-sensitive liposomes

Research Project

Project/Area Number 13557144
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

HONDA Yoshihiro  Department of Ophthalmology and Visual Science, Kyoto Univ., Professor, 医学研究科, 教授 (90026930)

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
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥9,800,000 (Direct Cost: ¥9,800,000)
Fiscal Year 2002: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2001: ¥5,900,000 (Direct Cost: ¥5,900,000)
Keywordsheat-sensitive liposomes / retinochoroid / micro circulation / drug delivery system / choroidal neovascularization / interferon / fluorescein fundus angiography / laser / ラット / 光線力学療法 / 脈絡膜血管 / 脈絡膜循環 / スリットランプ型光線力学装置 / 蛍光物質
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.

Report

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

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Kamizuru H 他: "Monoclonal antibody-mediated drug targeting to choroidal neovascularization in the rat"Invest Ophthalmol Vis Sci.. 42・11. 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 他: "Biodegradable scleral plugs for vitreoretinal drug delivery"Adv Drug Deliv Rev. 52. 25-36 (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 他: "Targeting of interferon to choroidal neovascularization by use of dextran and metal coordination"Invest Ophthalmol Vis Sci. 43・3. 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] Yasukawa T 他: "Effect of tranilast on proliferation, collagen gel contraction and transforming growth factor beta secretion of retinal pigment epithelial cells and fibroblasts"Ophthalmic Res.. 34. 206-212 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yasukawa T 他: "Sustained release of cis-hydroxyproline in the treatment of experimental proliferative vitreoretinopathy in rabbits"Graefe's Ophthalmol. 240. 672-678 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kamizuru H, Kimura H, Yasukawa T, Tabata Y, Honda Y, Ogura Y.: "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, Kimura H, Tabata Y, Ogura Y.: "Biodegradable scleral plugs for vitreoretinal drug delivery"Adv Drug Deliv Rev.. 52. 25-36 (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, Kimura H, Tabata Y, Kamizuru H, Miyamoto H, Honda Y, Ogura Y.: "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] Yasukawa T, Kimura H, Dong J, Tabata Y, Miyamoto H, Honda Y, Ogura Y.: "Effect of tranilast on proliferation, collagen gel contraction, and transforming growth factor beta secretion of retinal pigment epithelial cells and fibroblasts"Ophthalmic Res.. 34. 206-212 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yasukawa T, Kimura H, Tabata Y, Miyamoto H, Honda Y, Ogura Y.: "Sustained release of cishydroxyproline in the treatment of experimental proliferative vitreoretinopathy in rabbits"Graefe's Ophthalmol.. 240. 672-678 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kamizuru H他: "Monoclonal Antibody-Mediated Drug Targeting to Choroidal Neovascularization in the Rat"Invest Ophthalmol Vis Sci. 42・11. 2664-2672 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yasukawa T他: "Targeting of Interferon to Choroidal Neovascularization by Use of Dextran and Metal Coordination"Invest Ophthalmol Vis Sci. 43・3. 842-848 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yasukawa T他: "Sustained release of cis-hydroxyproline in the treatment of experimental proliferative vitreoretinopathy in rabbits"Grafes Arch Clin Exp Ophthalmol. 240・8. 672-678 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yasukawa T他: "Effect of Tranilast on Proliferation, Collagen Gel Contraction, and Transforming Growth Factor Beta Secretion of Retinal Pigment Epithelial Cells and Fibroblasts"Ophthalmic Res.. 34・4. 206-212 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nishijima K他: "In vivo evaluation of platelet-endothelial interactions after transient retinal ischemia"Invest Ophthalmol Vis Sci.. 42・9. 2102-2109 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nonaka A他: "Inflammatory Response after Scatter Laser Photocoagulation in Nonphotocoagulated Retina"Invest Ophthalmol Vis Sci.. 43・4. 1204-1209 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kiryu J 他: "Pars plana vitrectomy for cystoid macular edema secondary to sarcoid uveitis"Ophthalmology. 108. 1140-1144 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamashiro K 他: "Inhibitory effects of antithrombin III against leukocyte rolling and infiltration during endotoxin-induced uveitis in rats"Invest Ophthalmol Vis Sci. 42. 1553-1560 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nishijima K 他: "In vivo evaluation of platelet-endothelial interactions after transient retinal ischemia"Invest Ophthalmol Vis Sci. 42. 2102-2109 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nonaka A 他: "Inhibitory effect of ischemic preconditioning on leukocyte participation in retinal ischemia-reperfusion injury"Invest Ophthalmol Vis Sci. 42. 2380-2385 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamashiro K 他: "Suppressive effects of histamine H1 receptor antagonist diphenhydramine on the leukocyte infiltration during endotoxin-induced uveitis"Exp Eye Res. 73. 69-80 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nonaka A 他: "Scatter laser photocoagulation causes inflammatory response in unphotocoagulated retina"Invest Ophthalmol Vis Sci. (in press).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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