Non-Invasive Drug Delivery to Treat Posterior Uveitis

在美国，中间和后葡萄膜炎导致10%的失明。治疗的主要方法是根除感染原因，并用皮质类固醇或免疫抑制剂平息炎症。事实证明，将治疗浓度的抗炎药物输送到地球后部是困难的。有四种将化合物输送到后房的方法：玻璃体内注射、口服给药，然后通过视神经血流分布到眼睛内，球周注射，以及局部使用后通过巩膜被动扩散。每种方法都有众所周知的缺点。 该计划将研究兔眼后半部的非侵入性药物输送。具体目标包括研究皮质类固醇的被动渗透性和增强非侵入性经巩膜向后视网膜输送的机制。这些机制包括减少结膜和脉络膜视网膜前清除的方法。最后，一旦我们确定了最大限度地提供皮质类固醇的配方和条件，我们将在体内研究我们的技术在治疗兔模型内毒素诱导的葡萄膜炎中的有效性。

Intermediate and posterior uveitis cause 10% of blindness in the U.S. The mainstay of therapy is to eradicate the infectious cause and to quell the inflammation with corticosteroids or immunosuppressants. Delivery of anti-inflammatory drugs to the posterior portion of the globe in therapeutic concentrations has proven difficult. There are four methods of delivering compounds to the posterior chamber: intravitreal injection, oral administration with subsequent distribution into the eye through optic blood flow, peribulbar injection, and passive diffusion through the sclera following topical application. Each method has its well-known drawbacks. This proposal will study non-invasive drug delivery to the posterior portion of the rabbit's eye. Specific aims include studying the passive permeability of a corticosteroid and mechanisms to enhance non-invasive transscleral delivery to the posterior retina. Included in these mechanisms are means to decrease conjunctival and choroidal pre-retinal clearance. Lastly, once we have determined the formulation and conditions that maximize corticosteroid delivery, we will study in vivo effectiveness of our technique in the treatment of endotoxin-induced uveitis in the rabbit model.