I-Corps: Lens-mediated Delivery of Therapy for Dry Eye Disease

I-Corps：晶状体介导的干眼病治疗

• 批准号: 2348174
• 负责人: Bryan Brown
• 金额: $ 5万
• 依托单位: University of Pittsburgh
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-11-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2348174&HistoricalAwards=false
• 关键词: Corps; Lens; mediated; Delivery; Therapy; Corps; Lens; mediated; Delivery; Therapy

The broader impact/commercial potential of this I-Corps project is the development of technologies to treat dry eye disease. Current treatments for dry eye disease are largely limited to over-the-counter relief (artificial tears) or prescription medications targeting the adaptive immune system. Artificial tears do not address the cellular and inflammatory mechanisms of dry eye disease and do not offer long-term relief. Prescription medications broadly target T cell migration, proliferation, activation, and inflammatory mediator secretion. However, these treatments have side effects including burning, irritation, and blurry vision. They also require frequent instillation of drops, which, coupled with side effects, may result in treatment non- compliance. In addition, bolus delivery and medication loss are major limitations of eye drops, as the therapeutic agent is only in contact with the ocular surface for a short period, limiting efficacy. The proposed technology uses a dual immune and goblet cell fate modulator medication and improved drug delivery via a coating applied to soft contact lenses. A therapeutic that effectively addresses dry eye disease may improve patient outcomes.This I-Corps project is based on the development of a short-term, low-dose, single cytokine treatment for dry eye disease coupled with a contact lens-mediated delivery method. The proposed technology modulates both innate and adaptive immunity, and concurrently improves tear film stability by restoring goblet cell number and function. This approach includes the use of interleukin 4 (IL-4) as a dual immune and goblet cell fate modulator and improved drug delivery via a tunable nanoscale biopolymer coating applied to soft contact lenses. The proposed lens-mediated delivery technology includes an electrostatic layer by layer polymeric coating that complexes, protects, and steadily releases small amounts of cytokine at the ocular surface. This approach has the potential to provide increased efficacy over current approaches that seek symptomatic relief or inhibition of T cell activation broadly. In addition, the lens-mediated delivery vehicle has benefits over medicated eye drops as the coating may more effectively deliver IL-4 directly to the ocular surface.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该I-Corps项目的更广泛的影响/商业潜力是开发治疗干眼症的技术。目前针对干眼症的治疗在很大程度上仅限于针对适应性免疫系统的处方药（人造泪水）或处方药。人工眼泪不能解决干眼病的细胞和炎症机制，也不能长期缓解。处方药广泛针对T细胞迁移，增殖，激活和炎症介质分泌。但是，这些处理具有副作用，包括燃烧，刺激和视力模糊。他们还需要频繁滴注滴剂，再加上副作用，可能导致治疗不合规。此外，推注和药物损失是眼滴的主要局限性，因为治疗剂仅在短时间内与眼表接触，从而限制了功效。提出的技术使用双重免疫和杯状细胞命运调节剂药物，并通过涂层涂层涂在软接触镜片上。 一种有效解决干眼病的治疗性可以改善患者的结局。该I-Corps项目基于短期，低剂量的单细胞因子治疗的干燥眼病，并与隐形眼镜介导的递送方法相结合。 提出的技术可以调节先天和适应性免疫，并通过恢复杯状细胞数量和功能，同时改善撕裂膜的稳定性。 这种方法包括将白介素4（IL-4）用作双免疫和杯状细胞命运调节剂，并通过适用于软接触透镜的可调纳米级生物聚合物涂层改善药物递送。拟议的透镜介导的递送技术包括沿层聚合物涂层的静电层，该层在眼表面复合，保护和稳步释放少量的细胞因子。 这种方法具有与当前寻求症状缓解或抑制T细胞激活的当前方法相比，具有提高功效。 此外，透镜介导的送货工具比药物滴眼液具有好处，因为涂层可能会更有效地直接将IL-4直接传递到眼表。该奖项反映了NSF的法定任务，并且认为值得通过基金会的知识分子优点评估来支持，并具有更广泛的影响。