Transscleral Drug Delivery for Retinal Disorders

描述（由申请人提供）：埃默里大学眼科与佐治亚理工学院、内布拉斯加大学和宾夕法尼亚大学开展多学科合作。此次合作的目的是改善眼后段的药物输送。将药物递送至该靶点是视网膜疾病治疗中的重大挑战。眼球药物治疗的方法包括全身给药、滴眼剂和眼眶注射。这些技术可能会发生药物稀释、眼部感染、眼内炎和手术损伤（例如视网膜脱离）。鉴于这些缺点，我们假设经巩膜方法更适合后段药物输送。我们建议开发使用纳米颗粒、微针、纤维蛋白密封剂、本体透入和电穿孔的新型经巩膜药物递送方法。我们将a）检查经巩膜药物转运的生理学，b）建立分析方法来确定低分子量药物以及大分子药物在后段各个区域的分布，以及c）在实验动物模型中证明递送和治疗效果。在基础科学实验、临床前研究或临床研究中已知待测药物会影响视网膜疾病。 该项目需要来自眼科、工程和制药科学等不同学科的研究人员之间的合作研究。里程碑：第一年完成理论模型；这些将每年进行实验后重新评估。药物输送系统已经在体外建立，并且在第一年将产生用于模型细化的数据集，并为第一年和第二年的体内研究建立起始参数。毒性研究将在第二年和第三年完成。将在第三年至第五年收集药代动力学和药效学数据。第四年和第五年获得疗效数据。 通过完成这些临床前测试，我们将发现和开发有效地将药物输送到眼睛的新途径。这些递送技术应该比现有技术更安全、更有效。 最终，这些结果将指导我们加强眼科实践中的药物治疗。

DESCRIPTION (provided by applicant): The Ophthalmology Department at Emory University leads a multidisciplinary collaboration with the Georgia Institute of Technology, University of Nebraska, and University of Pennsylvania. This collaboration was formed to improve drug delivery to the posterior segment of the eye. Drug delivery to this target is a significant challenge in the treatment of retinal disorders. Methods for drug treatment of the globe include systemic administration, eye drops, and injection into the orbit. Drug dilution, ocular infection, endophthalmitis, and surgical damage such as retinal detachment can occur with these techniques. Given these drawbacks, we hypothesize that transscleral approaches are better for posterior segment drug delivery. We propose to develop novel transscleral drug delivery approaches that use nanoparticles, microneedles, fibrin sealant, ontophoresis, and electoporation. We will a) examine the physiology of transscleral drug transport, b) establish analytical methods to determine the distribution of low molecular weight drugs as well as macromolecules to the various regions of the posterior segment, and c) demonstrate delivery and therapeutic effectiveness in experimental animal models. The drugs to be tested are known to affect retinal diseases in basic science experiments, pre-clinical studies, or clinical studies. This project entails collaborative research among investigators from various disciplines including ophthalmology, engineering, and pharmaceutical sciences. Milestones: Theoretical models will be completed during the first year; these will be post-experimentally reassessed annually. Drug delivery systems are established in vitro already, and during the first year will produce data sets for model refinement and establish starting parameters for in vivo studies in the first and second years. Toxicity studies will be completed during the second and third years. Pharmacokinetic and pharmacodynamic data will be collected during the third through fifth years. In the fourth and fifth years efficacy data are obtained. By accomplishing these pre-clinical tests, we will discover and develop new routes for efficacious delivery of drugs to the eye. These delivery techniques should be safer and more effective than the state of the art. Ultimately, these results will guide us in enhancing drug treatments in ophthalmic practice.