Systemic nanotherapies for ocular inflammation and choroidal neovascularization.

用于眼部炎症和脉络膜新生血管形成的全身纳米疗法。

基本信息

  • 批准号:
    8861816
  • 负责人:
  • 金额:
    $ 40.5万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-05-01 至 2019-04-30
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Age-related macular degeneration (AMD) is the leading cause of blindness in older people. Inflammation, mediated by activated microglia/macrophages (mi/ma), plays a key role in the pathogenesis of both geographic atrophy and exudative AMD, in humans and in animal models. Development of systemic drug delivery approaches targeting these cells to treat ocular inflammation and choroidal neovascularization (CNV), can have significant benefits, in addition to providing insights on the role of mi/ma on AMD therapy. Such therapies may improve patient compliance, reduce side effects arising from intravitreal implants and free drugs, reduce costs, and allow therapies during early stages of AMD. Understanding and utilizing the transport of nanoparticles from blood to the choroid/retina may provide new avenues for systemic drug delivery. We explored globular, polyamidoamine (PAMAM) dendrimers, with favorable physicochemical attributes. Our preliminary results in a lipid-induced rat dry/wet AMD model demonstrate that systemic hydroxyl-functionalized PAMAM dendrimers: (1) can target activated mi/ma in the areas of choroidal neovascularization and retinal inflammation, and be selectively retained for a sustained period of time; (2) can deliver anti-inflammatory, anti- oxidant N-acetyl cysteine (NAC) to attenuate proinflammatory cytokines, and cause significant CNV suppression, when administered in early stages (day 3 after lipid, `dry' AMD); (3) deliver a combination of NAC and triamcinolone acetonide (TA), to cause CNV regression, when administered in late stages (day 11 after lipid, `wet' AMD); We explore three aims: (1) Determine whether systemic dendrimer-drug conjugates selectively localize and retain in activated microglia/macrophages in the choroid/retina, and whether an increase in dendrimer size improves such localization and retention in the rat AMD model. (2) Determine the ocular toxicity of the systemic dendrimer vehicle in healthy rats, and characterize pharmacokinetics and biodistribution of the conjugated drugs in the rat CNV model. (3) Determine if systemically administered D-NAC and/or D-TA conjugates attenuate inflammation, suppress and cause regression of CNV in the rat AMD model. If successful, these studies offer potential for targeted therapies for dry/wet AMD, and broad clinical adaptation.


项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(2)

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Kannan Rangaramanujam其他文献

Kannan Rangaramanujam的其他文献

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{{ truncateString('Kannan Rangaramanujam', 18)}}的其他基金

Systemic nanotherapies for ocular inflammation and choroidal neovascularization.
用于眼部炎症和脉络膜新生血管形成的全身纳米疗法。
  • 批准号:
    9052766
  • 财政年份:
    2015
  • 资助金额:
    $ 40.5万
  • 项目类别:
Nanotherapies for the treatment of neurodevelopmental disorders.
用于治疗神经发育障碍的纳米疗法。
  • 批准号:
    8671529
  • 财政年份:
    2014
  • 资助金额:
    $ 40.5万
  • 项目类别:
Postnatal combination therapy for cerebral palsy
脑瘫产后联合治疗
  • 批准号:
    8694873
  • 财政年份:
    2014
  • 资助金额:
    $ 40.5万
  • 项目类别:
Nanotherapies for the treatment of neurodevelopmental disorders.
用于治疗神经发育障碍的纳米疗法。
  • 批准号:
    8826117
  • 财政年份:
    2014
  • 资助金额:
    $ 40.5万
  • 项目类别:
Postnatal combination therapy for cerebral palsy
脑瘫产后联合治疗
  • 批准号:
    9270042
  • 财政年份:
    2014
  • 资助金额:
    $ 40.5万
  • 项目类别:
Nanotherapies for the treatment of neurodevelopmental disorders.
用于治疗神经发育障碍的纳米疗法。
  • 批准号:
    9257381
  • 财政年份:
    2014
  • 资助金额:
    $ 40.5万
  • 项目类别:
Drug Delivery and Nanotechnology Module
药物输送和纳米技术模块
  • 批准号:
    10256789
  • 财政年份:
    1997
  • 资助金额:
    $ 40.5万
  • 项目类别:
Drug Delivery and Nanotechnology Module
药物输送和纳米技术模块
  • 批准号:
    10020647
  • 财政年份:
    1997
  • 资助金额:
    $ 40.5万
  • 项目类别:
Drug Delivery and Nanotechnology Module
药物输送和纳米技术模块
  • 批准号:
    10700932
  • 财政年份:
    1997
  • 资助金额:
    $ 40.5万
  • 项目类别:
Drug Delivery and Nanotechnology Module
药物输送和纳米技术模块
  • 批准号:
    9795551
  • 财政年份:
  • 资助金额:
    $ 40.5万
  • 项目类别:

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