Nanogels for Drug Delivery across the BRB to Treat Diabetic Retinopathy

纳米凝胶通过 BRB 输送药物治疗糖尿病视网膜病变

基本信息

  • 批准号:
    10000203
  • 负责人:
  • 金额:
    $ 38.63万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-09-01 至 2023-08-31
  • 项目状态:
    已结题

项目摘要

While new therapeutics, especially protein drugs such as Avastin, Lucentis and growth factors, are being developed for treating retinal diseases, such as diabetic retinopathy and macular degeneration, the use of these therapeutics is still hampered by the need for more effective method of delivery. The reason is that these therapeutics have short half-lives, do not or hardly cross the blood retinal barrier (BRB), and can cause toxicity and side effects at high dose. Nanoparticles show great promise for transporting drugs across biological barriers, reducing drug clearance, and improving the bioavailability of drugs at targets. However, no nanoparticles have been developed to effectively deliver drugs across the BRB yet. The long-range goal of this project is to develop novel nanoparticles for long-term release of therapeutics across the BRB to treat retinal diseases. The immediate objective is to develop unique subconjunctivally injectable, thermoresponsive and biodegradable nanogels for aqueous loading, enhanced stability and BRB permeability, and sustained release of protein drugs to treat early diabetic retinopathy. For this specific objective, we will use insulin as a model protein drug for the development of the nanogel drug delivery platform because insulin is a survival factor for endothelial and neural cells, and plays an important role in retinal function. The hypothesis of the proposal is that subconjunctivally injectable nanogels with tailored balance of hydrophilicity, hydrophobicity, charge content and hydrolytic degradation properties, can act as an effective local delivery system platform for sustained release of therapeutics such as insulin across the BRB to protect retinal cells from apoptosis and improve vascular leakage in diabetes. Three specific aims are: 1) in vitro optimization and characterization of nanogels for aqueous loading, enhanced stability, and sustained release of insulin; 2) in vitro and ex vivo optimization and characterization of nanogels for enhanced insulin permeability across the sclera and the BRB; and 3) in vitro bioeffect, and in vivo pharmacokinetics and bioeffect evaluations of subconjunctivally injected insulin-loaded nanogels. The proposed nanogels are physicochemically, biologically, clinically and collaboratively innovative, and will provide a novel periocular drug delivery platform for enhancing drug permeability across the BRB and achieving long-term drug bioavailability in the retina to treat diabetic retinopathy and other retinal diseases.
而新的治疗方法,特别是蛋白质药物,如阿瓦斯汀,Lucentis和生长因子,正在被开发

项目成果

期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Design strategies for physical-stimuli-responsive programmable nanotherapeutics.
  • DOI:
    10.1016/j.drudis.2018.04.003
  • 发表时间:
    2018-05
  • 期刊:
  • 影响因子:
    7.4
  • 作者:
    Sahle FF;Gulfam M;Lowe TL
  • 通讯作者:
    Lowe TL
Design strategies for chemical-stimuli-responsive programmable nanotherapeutics.
  • DOI:
    10.1016/j.drudis.2018.09.019
  • 发表时间:
    2019-01
  • 期刊:
  • 影响因子:
    7.4
  • 作者:
    Gulfam M;Sahle FF;Lowe TL
  • 通讯作者:
    Lowe TL
Nanotechnology enabled regenerative medicine for neurological disorders.
纳米技术使神经系统疾病的再生医学成为可能。
  • DOI:
    10.1016/j.addr.2019.11.006
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    16.1
  • 作者:
    Lowe,TaoL;Agrahari,Vivek;Kannan,RangaramanujamM;Kannan,Sujatha
  • 通讯作者:
    Kannan,Sujatha
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Tao L Lowe其他文献

Tao L Lowe的其他文献

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{{ truncateString('Tao L Lowe', 18)}}的其他基金

Nanogels for Drug Delivery across the BRB to Treat Diabetic Retinopathy
纳米凝胶通过 BRB 输送药物治疗糖尿病视网膜病变
  • 批准号:
    10151048
  • 财政年份:
    2016
  • 资助金额:
    $ 38.63万
  • 项目类别:
Nanogels for Drug Delivery across the BRB to Treat Diabetic Retinopathy
纳米凝胶通过 BRB 输送药物治疗糖尿病视网膜病变
  • 批准号:
    9547439
  • 财政年份:
    2016
  • 资助金额:
    $ 38.63万
  • 项目类别:
Nanogels for Drug Delivery across the BRB to Treat Diabetic Retinopathy
纳米凝胶通过 BRB 输送药物治疗糖尿病视网膜病变
  • 批准号:
    9197096
  • 财政年份:
    2016
  • 资助金额:
    $ 38.63万
  • 项目类别:
Nanogels for Drug Delivery across the BRB to Treat Diabetic Retinopathy
纳米凝胶通过 BRB 输送药物治疗糖尿病视网膜病变
  • 批准号:
    9329464
  • 财政年份:
    2016
  • 资助金额:
    $ 38.63万
  • 项目类别:
Hydrogels for Periocular Drug Delivery to Treat Diabetic Retinopathy
用于眼周药物递送的水凝胶治疗糖尿病视网膜病
  • 批准号:
    7472429
  • 财政年份:
    2007
  • 资助金额:
    $ 38.63万
  • 项目类别:
Hydrogels for Periocular Drug Delivery to Treat Diabetic Retinopathy
用于眼周药物递送的水凝胶治疗糖尿病视网膜病
  • 批准号:
    7314789
  • 财政年份:
    2007
  • 资助金额:
    $ 38.63万
  • 项目类别:
Hydrogels for Periocular Drug Delivery to Treat Diabetic Retinopathy
用于眼周药物递送的水凝胶治疗糖尿病视网膜病
  • 批准号:
    7867291
  • 财政年份:
    2007
  • 资助金额:
    $ 38.63万
  • 项目类别:

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