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Engineered multi-therapeutic agents delivery system towards retinal ganglion cell axon regeneration

Engineered multi-therapeutic agents delivery system towards retinal ganglion cell axon regeneration
针对视网膜神经节细胞轴突再生的工程化多治疗药物递送系统
批准号:
10394885
负责人:
Dae Won Park
金额:
$37.28万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-05-01 至 2024-04-30

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中文摘要
翻译
项目总结 在美国,大约有220万人患有视神经疾病,占世界人口的9%到12% 所有的失明病例。其中,接受适当治疗的患者中有10%继续经历 视力丧失,这显然需要一个替代的治疗策略。 目前的治疗方法之一是利用神经营养因子(NTF)来增加视网膜神经节细胞(RGC)。 生存,负责视觉功能。而通过玻璃体内注射直接给药NTF则有 已经取得了一些成功,但对这些NTF变性的敏感性限制了它的临床成功。另外,送货 由于视神经病变伴有神经变性,仅使用NTF可能会导致有限的治疗成功, 由神经毒性循环引起。 为了解决这些问题,我们设计了模拟带负电荷的聚合物纳米粒子。 天然肝素中的磺酸盐基团并提供多种治疗剂以连续供应NTFS和 抑制神经毒性。我们的策略的优势包括:1)在目标站点持续递送NTF, 模拟NTF的连续传输,2)系统中包裹的NTF的生物活性延长,以及3) 持续输送抗神经毒剂,持续抑制神经变性 视神经疾病的进展。 我们在两个特定目标下构建了此应用程序:(1)确定适当的 用于多种治疗药物共给药的纳米粒制剂和(2)评价RGC轴突 大鼠视神经挤压模型的再生。
英文摘要
PROJECT SUMMARY In the U.S., approximately 2.2 million people suffer from optic neuropathies, accounting for 9 to 12% of all cases of blindness. Of them, 10% of patients that receive proper medical treatment continue to experience vision loss, which obviously needs an alternative treatment strategy. One of current treatments utilizes neurotrophic factors (NTFs) to increase retinal ganglion cell (RGC) survival, responsible for the visual function. While direct administration of NTFs via intravitreal injection has had some success, a susceptibility to denaturation of these NTFs limits its clinical success. Also, the delivery of NTFs alone may result in limited treatment success since optic neuropathies accompany neurodegeneration, caused by the neurotoxic cycles. To resolve these problems, we have engineered polymeric nanoparticles that mimic negatively charged sulfonate groups in natural heparin and deliver multiple therapeutic agents to continuously supply NTFs and inhibit the neurotoxicity. The advantages of our strategy include: 1) sustained delivery of NTFs at target site, mimicking continuous NTF transport, 2) prolonged bioactivity of NTFs encapsulated in the system and 3) sustained delivery of an anti-neurotoxic agent, continuously inhibiting neurodegeneration during the progression of optic neuropathies. We have constructed this application under two specific aims: (1) determine an appropriate nanoparticle formulation for the co-delivery of the multiple therapeutic agents and (2) evaluate RGC axon regeneration in rat optic nerve crush model.
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Engineered multi-therapeutic agents delivery system towards retinal ganglion cell axon regeneration
  • 批准号:
    10615620
  • 项目类别:
  • 资助金额:
    $38.43万
  • 财政年份:
    2020
  • 负责人:
    Dae Won Park
  • 依托单位:
A Functional Reverse Thermal Gel for Retinal Ganglion Cell Axon Regeneration
  • 批准号:
    9087269
  • 项目类别:
  • 资助金额:
    $18.91万
  • 财政年份:
    2015
  • 负责人:
    Dae Won Park
  • 依托单位:
A biomimetic reverse thermal gel for the treatment of myocardial infarction
  • 批准号:
    8761159
  • 项目类别:
  • 资助金额:
    $21.49万
  • 财政年份:
    2014
  • 负责人:
    Dae Won Park
  • 依托单位:
海外基金