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

这个i-Corps项目的更广泛的影响/商业潜力是开发治疗干眼病的技术。目前干眼病的治疗方法主要限于非处方药缓解(人工泪水)或针对适应性免疫系统的处方药。人工泪水不能解决干眼症的细胞和炎症机制，也不能提供长期缓解。处方药主要针对T细胞的迁移、增殖、激活和炎症介质的分泌。然而，这些治疗有副作用，包括灼热、刺激和视力模糊。它们还需要频繁滴注，再加上副作用，可能会导致治疗不依从。此外，滴眼剂的主要局限性是给药和药物损失，因为治疗剂只与眼表短期接触，限制了疗效。这项拟议的技术使用了双重免疫和杯状细胞命运调节剂药物，并通过应用于软性隐形眼镜的涂层改善了药物输送。一种有效治疗干眼症的疗法可能会改善患者的预后。这个I-Corps项目是基于开发一种短期、低剂量、单一细胞因子治疗干眼病的方法，并结合隐形眼镜介导的给药方法。该技术同时调节天然免疫和获得性免疫，同时通过恢复杯状细胞的数量和功能来改善泪膜的稳定性。这种方法包括使用白细胞介素4(IL-4)作为双重免疫和杯状细胞命运调节剂，以及通过应用于软性隐形眼镜的可调纳米生物聚合物涂层来改善药物输送。所提出的晶状体介导的递送技术包括一层又一层的静电聚合物涂层，该涂层可以在眼表面复合、保护并稳定地释放少量的细胞因子。与目前广泛寻求缓解症状或抑制T细胞激活的方法相比，这种方法有可能提供更高的疗效。此外，镜片介导的载体比药物眼药水有好处，因为涂层可以更有效地将IL-4直接输送到眼表。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.