Identification of eye-homing peptides and their use for targeted liposomal drug delivery in posterior uveitis

眼归巢肽的鉴定及其在后葡萄膜炎靶向脂质体药物递送中的应用

基本信息

  • 批准号:
    10612913
  • 负责人:
  • 金额:
    $ 19.31万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-05-01 至 2025-04-30
  • 项目状态:
    未结题

项目摘要

Human posterior segment uveitis of autoimmune origin is a chronic disease that can impair vision and result in blindness. A variety of autoantigens, including interphotoreceptor retinoid binding protein (IRBP), have been implicated in uveitis pathogenesis. The T cells reactive against these antigens access the eye through the blood-retinal barrier and cause local inflammation and tissue damage. Two of the main challenges in non- infectious posterior uveitis are – 1) to define the molecular changes induced during uveitis in endothelium of the choroidal and retinal vasculature, and 2) to devise novel ways to direct the systemically-administered drugs primarily into the eye to enhance their efficacy but minimize adverse effects. We hypothesize that the vascular endothelium of the eye in uveitis is characterized by unique molecular markers that facilitate both selective migration of the pathogenic T cells into the target organ and cellular interaction with the inducers/ mediators of inflammation and tissue damage. Accordingly, the identification of peptide ligands (by phage peptide library screening) that interact with such markers would be invaluable tools to study disease pathogenesis. Furthermore, these peptide ligands can be exploited for targeted drug delivery to the eye with the objective of enhancing efficacy, but reducing systemic toxicity of those drugs. In collaboration with Dr. Erkki Ruoslahti (Sanford-Burnham, La Jolla), who pioneered the concept of vascular ‘address molecules’ or ‘zip codes’, we published a study on the molecular profiling of the synovial vasculature in adjuvant arthritis in rats (PNAS 2011). We identified unique joint-homing peptide ligands using an innovative approach of ex vivo/ in vivo enrichment of clones from a phage peptide-display library. Recently, we also reported CNS-homing peptides in the EAE model of human multiple sclerosis. The advantage of using phages to detect tissue-specific markers is that there is no a priori bias in predicting the peptide sequences/motifs. And, unlike antibodies, phage peptides interact with functional domains of target molecules. We now plan to apply this methodology to rat experimental autoimmune uveitis (EAU). The aims of our study in collaboration with experts in EAU (Dr. Caspi and Dr. Sun), [in vascular biology (Dr. Teesalu from Ruoslahti group), and in pharmacodynamics (Dr. Swaan)] are: Aim 1. To identify peptide ligands homing to the diseased eye in EAU using the ex vivo/ in vivo screening of phage peptide library. (a) To identify unique peptide-encoding phages that home to the vasculature and retina of the diseased eye; and (b) to determine the relative specificity of select phages/ peptides [for other tissues within the eye as well as other organs in EAU versus control (healthy/EAE) rats.] Aim 2. To use the eye-homing peptides for targeted drug delivery to the diseased sites in EAU. To use a specific peptide to guide liposomes encapsulating a drug (e.g., methotrexate) [to the diseased sites in eyes in EAU, and compare the pharmacodynamics and safety of that drug] with that using plain liposomes or free drug. The results would advance understanding of pathogenesis of human uveitis and designing of novel therapies.
自体免疫源性人后段葡萄膜炎是一种慢性疾病,可损害视力和视力

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(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

KAMAL D MOUDGIL其他文献

KAMAL D MOUDGIL的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('KAMAL D MOUDGIL', 18)}}的其他基金

Validation of the joint-homing and drug delivery attributes of novel peptides in a mouse arthritis model
在小鼠关节炎模型中验证新型肽的关节归巢和药物递送特性
  • 批准号:
    10589192
  • 财政年份:
    2023
  • 资助金额:
    $ 19.31万
  • 项目类别:
Identification of eye-homing peptides and their use for targeted liposomal drug delivery in posterior uveitis
眼归巢肽的鉴定及其在后葡萄膜炎靶向脂质体药物递送中的应用
  • 批准号:
    10452321
  • 财政年份:
    2022
  • 资助金额:
    $ 19.31万
  • 项目类别:
Anti-arthritic activity and therapeutic use of novel joint-homing peptides
新型关节归巢肽的抗关节炎活性和治疗用途
  • 批准号:
    8998611
  • 财政年份:
    2015
  • 资助金额:
    $ 19.31万
  • 项目类别:
Anti-arthritic activity and therapeutic use of novel joint-homing peptides
新型关节归巢肽的抗关节炎活性和治疗用途
  • 批准号:
    9339552
  • 财政年份:
    2015
  • 资助金额:
    $ 19.31万
  • 项目类别:
Identification of CNS-homing peptides for therapeutic use in multiple sclerosis
鉴定用于治疗多发性硬化症的中枢神经系统归巢肽
  • 批准号:
    8897016
  • 财政年份:
    2013
  • 资助金额:
    $ 19.31万
  • 项目类别:
Identification of CNS-homing peptides for therapeutic use in multiple sclerosis
鉴定用于治疗多发性硬化症的中枢神经系统归巢肽
  • 批准号:
    8638421
  • 财政年份:
    2013
  • 资助金额:
    $ 19.31万
  • 项目类别:
Defining glomerulus-homing peptides for targeted drug delivery in lupus nephritis
定义用于狼疮性肾炎靶向药物递送的肾小球归巢肽
  • 批准号:
    8787075
  • 财政年份:
    2013
  • 资助金额:
    $ 19.31万
  • 项目类别:
Immune Modulation of Autoimmunity by Herbal Products
草药产品对自身免疫的免疫调节
  • 批准号:
    8290064
  • 财政年份:
    2009
  • 资助金额:
    $ 19.31万
  • 项目类别:
Immune Modulation of Autoimmunity by Herbal Products
草药产品对自身免疫的免疫调节
  • 批准号:
    8103241
  • 财政年份:
    2009
  • 资助金额:
    $ 19.31万
  • 项目类别:
Immune Modulation of Autoimmunity by Herbal Products
草药产品对自身免疫的免疫调节
  • 批准号:
    7898955
  • 财政年份:
    2009
  • 资助金额:
    $ 19.31万
  • 项目类别:

相似海外基金

Glutamine, dietary fiber, oligosaccharide and Bifidobacterium lungum exert symbiotic effects on adjuvant arthritis in rats.
谷氨酰胺、膳食纤维、低聚糖和肺双歧杆菌对大鼠佐剂性关节炎发挥共生作用。
  • 批准号:
    26350157
  • 财政年份:
    2014
  • 资助金额:
    $ 19.31万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
PATHOGENESIS OF ADJUVANT ARTHRITIS
佐剂性关节炎的发病机制
  • 批准号:
    3151647
  • 财政年份:
    1983
  • 资助金额:
    $ 19.31万
  • 项目类别:
EFFECT OF AUTOREACTIVE CELL LINES ON ADJUVANT ARTHRITIS
自身反应细胞系对佐剂性关节炎的影响
  • 批准号:
    3952965
  • 财政年份:
  • 资助金额:
    $ 19.31万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了