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Development of drug delivery system for choroidal neo-vasculization(CNV) using biodegradable high molecular implant

Research Project

Project/Area Number 15390528
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionKawasaki Medical School (2005)
Kyoto University (2003-2004)

Principal Investigator

KIRYU Junichi  Kawasaki medical school, Department of Ophthalmology, Professor, 医学部, 教授 (80281096)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Masayo  Kyoto university, Department of Ophthalmology, Associate professor, 医学研究科, 助教授 (80252443)
MIYAMOTO Kazuaki  Kyoto university, Department of Ophthalmology, Assistant, 医学研究科, 助手 (90359810)
TABATA Yasuhiko  Kyoto university, Department of Biomaterial, Professor, 再生医科学研究所, 教授 (50211371)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 2005: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥6,000,000 (Direct Cost: ¥6,000,000)
Keywordsage-related macular degeneration / choroidal neovasculization / biodegradable high molecular implant / drug delivery system / ゼラチン / 等電点 / ステロイド / 網膜硝子体界面 / 硝子体内投与 / ドラッグデリバリーシステム / ゼラチンマイクロスフェア / 塩基性線維芽細胞増殖因子 / インターフェロンβ / ポリ乳酸粒子 / 網膜下ドラッグデリバリーシステム
Research Abstract

Treatment with interferon β(INFβ) for diseases caused by choroidal neovasuculization(CNV) such as age related macular degeneration (AMD) was previously investigated.
However, eye drops and systemically administered drugs cannot deliver therapeutic drug concentrations into vitreoretinal tissue and they cause systemic side effects. We developed a drug delivery system for the biodegradable implant of INF(3 with specific effects on CNV that had no systemic side effects.
We developed biodegradable gelatin microspheres to which glutaraldehyde was added through alkarine and acid processes. Then we added basic fibroblast growth factor (bFGF) to these microspheres. These microspheres we investigated into the subretinal space of CNV models. After that, we implanted the microsphere complex with INFβ into the vitreal space (vitreal IFNβ injection group) or the subretinal space (subretinal IFNβ injection group). We estimated the time course of CNV changes in each group by ophthalmoscopy and fluorescein angiography.
In the control group (n=2), CNV appeared two weeks after implantation, and it continue grow until four to eight weeks after implantation. Then, the CNV diminished. The time courses of CNV growth in vitreal IFNβ injection group(n=2) and microsphere group (the group into which only gelatin microspheres were implanted in the subretinal space, n=2) were similar to that of the control group. However, in the subretinal IFNβ injection group(n=2), CNV did not diminish, and we found evidence of proliferative vitreous retinopathy(PVR).
We created CNV models into which gelatin microspheres with bFGF were implanted in the subretinal space. Vitreal IFNβ injection group and microsphere group showed no signs of recovery. More study of the CNV is needed in the future.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (25 results)

All 2006 2005 2004 Other

All Journal Article (21 results) Publications (4 results)

  • [Journal Article] Drug delivery from ocular implants.2006

    • Author(s)
      Yasukawa T 他
    • Journal Title

      Expert Opin Drug Deliv. 3(2)

      Pages: 261-273

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Drug delivery from ocular implants.2006

    • Author(s)
      Yasukawa T, Ogura Y, Tabata Y, et al.
    • Journal Title

      Expert Opin Drug Deliv. 3(2)

      Pages: 261-273

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Intraocular sustained drug delivery using implantable polymeric devices.2006

    • Author(s)
      Yasukawa T 他
    • Journal Title

      Adv Drug Deliv Rev. 57(14)

      Pages: 2033-2046

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Intraocular sustained drug delivery using implantable polymeric devices.2005

    • Author(s)
      Yasukawa T 他
    • Journal Title

      Adv Drug Deliv Rev. 57(14)

      Pages: 2033-46

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Drug delivery system using microspheres that contain tacrolimus in porcine small bowel transplantation.2005

    • Author(s)
      Eshita Y 他
    • Journal Title

      Transpl Int 17(12)

      Pages: 841-7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina.2005

    • Author(s)
      Tamura H 他
    • Journal Title

      Invest Ophthalmol Vis Sci. 46(4)

      Pages: 1440-4

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Erythropoietin as a retinal angiogenic factor in prolifer ative diabetic retinopathy.2005

    • Author(s)
      Watanabe D 他
    • Journal Title

      N Engl J Med. 353(8)

      Pages: 782-92

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Efficacy of surgical removal of the internal limiting membrane in diabetic cystoid macular edema.2005

    • Author(s)
      Kimura T 他
    • Journal Title

      Retina 25(4)

      Pages: 454-61

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Intraocular sustained drug delivery using implantable polymeric devices.2005

    • Author(s)
      Yasukawa T, Ogura Y, Tabata Y, et al.
    • Journal Title

      Adv Drug Deliv Rev. 57(14)

      Pages: 2033-2046

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Drug delivery system using microspheres that contain tacrolimus in porcine small bowel transplantation.2005

    • Author(s)
      Eshita Y, Uemoto S, Tabata Y, et al.
    • Journal Title

      Transpl Int. 17(12)

      Pages: 841-847

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina.2005

    • Author(s)
      Tamura H, Kiryu J, Yoshimura N et al.
    • Journal Title

      Invest Ophthalmol Vis Sci. 46(4)

      Pages: 1440-1444

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Erythropoietin as a retinal angiogenic factor in proliferative diabetic retinopathy.2005

    • Author(s)
      Watanabe D, Kiryu J, Yoshimura N.et al.
    • Journal Title

      N Engl J Med. 353(8)

      Pages: 782-792

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Efficacy of surgical removal of the internal limiting membrane in diabetic cystoid macular edema.2005

    • Author(s)
      Kimura T, Kiryu J, Takagi H, et al.
    • Journal Title

      Retina. 25(4)

      Pages: 454-461

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Drug delivery system using microspheres that contain tacrolimus in porcine small bowel transplantation.2005

    • Author(s)
      Eashita Y 他
    • Journal Title

      Transpl Int. 17(12)

      Pages: 841-847

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Erythropoietin as a retinal angiogenic factor in proliferative diabetic retinopathy.2005

    • Author(s)
      Watanabe D 他
    • Journal Title

      N Engl J Med. 353(8)

      Pages: 782-792

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Platelets adhering to the vascular wall mediate postischemic leukocyte-endothelial cell interactions in retinal microcirculation2004

    • Author(s)
      Nishijima K, Kiryu J, Tsujikawa A, et al.
    • Journal Title

      Investigative Ophthalmology and Visual Science 45

      Pages: 977-984

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Simvastatin inhibits leukocyte accumulation and vascular permeability in the retinas of rats with streptozotocin-induced diabetes2004

    • Author(s)
      Miyahara S, Kiryu J, Yamashiro K, et al.
    • Journal Title

      American Journal of Pathology 164

      Pages: 1697-1706

    • Related Report
      2004 Annual Research Report
  • [Journal Article] In vivo evaluation of retinal injury after transient ischemia in hypertensive rats2004

    • Author(s)
      Hirose F, Kiryu J, Miyamoto K, et al.
    • Journal Title

      Hypertension 43

      Pages: 1098-1102

    • Related Report
      2004 Annual Research Report
  • [Journal Article] In vivo three-dimensional evaluation of leukocyte behavior in retinal microcirculation of mice2004

    • Author(s)
      Miyahara S, Kiryu J, Miyamoto K, et al.
    • Journal Title

      Investigative Ophthalmology and Visual Science 45

      Pages: 4197-4201

    • Related Report
      2004 Annual Research Report
  • [Journal Article] In vivo evaluation of ocular inflammatory responses in experimental diabetes

    • Author(s)
      Tamura H, Kiryu J, Miyamoto K, et al.
    • Journal Title

      British Journal of Ophthalmology (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina

    • Author(s)
      Tamura H, Miyamoto K, Kiryu J, et al.
    • Journal Title

      Investigative Ophthalmology and Visual Science (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Publications] Miyahara S, Kiryu J, et al.: "Argatroban attenuates leukocyte- and platelet-endothelial cell interactions after transient retinal ischemia"Stroke. 34. 2043-2049 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishijima K, Kiryu J, et al.: "Platelets adhered to vascular wall mediate postischemic leukocyte-endothelial cell interactions in retinal microcirculation"Investigative Ophthalmolozy and Visual Science. 45. 977-987 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miyahara S, Kiryu J, et al.: "Simvastatin inhibits leukocyte accumulation and vascular permeability in the retinas of rats with streptozotocin-induced diabetes"American Journal of Pathology. (印刷中).

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirose F, Kiryu J, et al.: "In vivo evaluation of retinal injury after transient ischemia in hypertensive rats"Hypertension. (印刷中).

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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