Suprachroidal Drug Delivery for Retina Disorders

玻璃体内注射已成为眼后部药物输送的标准护理。虽然这件事 方法给药到眼睛，它不针对眼睛内的药物输送到治疗部位 行动，特别是在脉络膜和视网膜。这会导致药物使用效率低下，并可能产生副作用 非靶点，尤其是前段。此外，反复玻璃体内注射也与 副作用包括眼内炎、视网膜脱离和白内障。 在这项建议中，我们寻求通过以下方式将药物输送到脉络膜和视网膜的治疗作用部位 使用微针将药物注入脉络膜上腔(SCS)。南海是一个潜在的空间 巩膜和脉络膜之间，可以选择性地以微创的方式使用 一种长达数百微米的微针。靶向进入SCS的药物沐浴在脉络膜表面 和邻近的视网膜，而不是像玻璃体内注射后那样，将药物分布到后部 注射。一些研究，主要来自我们的实验室，已经证明了将药物输送到SCS的可行性。 这一多学科项目将首次深入研究脉络膜上药物的靶向给药。 微针，从而开发新的药物输送技术，为临床翻译奠定了基础。 本项目将研究向SCS输送药物以改善脉络膜新生血管(CNV)的治疗。 与老年性黄斑变性(AMD)有关，AMD是老年人失明的主要原因 老年人。我们将研究广泛应用于临床的大分子抗体药物贝伐单抗的用药。 用于这一适应症，以及帕佐帕尼，一种正在研究中的治疗CNV的小分子、抗血管生成药物。 我们的初步研究表明，SCS给药提供了更好的组织特异性靶向。 到后段，尤其是脉络膜和邻近的视网膜。基于这些发现，我们的长期- 学期目标是开发比玻璃体内注射更好的微创、靶向给药方法。 注射，以提高药物疗效，同时将药物和注射相关的副作用降至最低 CNV.在这项研究中，我们将检验这一假设，即脉络膜上腔给药提供了一条安全的途径 持续有效地给药治疗CNV等后节疾病。该项目已 三个具体目标：1)设计和制造一种微创微针装置，并测定其效果 有针对性的脉络膜上腔注射。2)测定药物的理化性质和缓释效果。 释放剂型对药物在眼后组织中的药代动力学和生物分布的影响 脉络膜上腔分娩。3)确定脉络膜上腔小分子给药的有效性和安全性 用于脉络膜新生血管缓释治疗的药物和高分子药物。除了……之外 改进CNV治疗，该项目的成果将为治疗其他疾病提供创新的针对性解决方案 后节病变包括糖尿病视网膜病变、干性黄斑变性、视网膜色素变性和葡萄膜炎。

Intravitreal injection has become the standard of care for drug delivery to the back of the eye. While this method administers drug to the eye, it does not target drug delivery within the eye to the sites of therapeutic action, specifically in the choroid and retina. This leads to inefficient use of the drug and possible side effects at off-target sites, especially in the anterior segment. Moreover, repeated intravitreal injections are associated with side effects including endophthalmitis, retinal detachment, and cataracts. In this proposal, we seek to target drug delivery to the sites of therapeutic action in choroid and retina by injecting drugs into the suprachoroidal space (SCS) using a microneedle. The SCS is a potential space between sclera and choroid that can be accessed selectively and in a minimally invasive way using a microneedle measuring hundreds of microns long. Drug targeted into the SCS bathes the choroidal surface and adjacent retina, rather than distributing drug throughout the posterior segment, as occurs after intravitreal injection. A few studies, mostly from our laboratories, have demonstrated feasibility of drug delivery to SCS. This multidisciplinary project will provide the first in-depth study of suprachoroidal drug delivery targeted using microneedles and thereby develop novel drug delivery technologies that set the stage for clinical translation. This project will study drug delivery to the SCS to improve treatment of choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD), which is the leading cause of blindness in the elderly. We will study administration of bevacizumab, a macromolecular antibody drug in widespread clinical use for this indication, and pazopanib, a small-molecule, anti-angiogenic drug under investigation to treat CNV. Our preliminary studies indicate that drug administration to the SCS offers superior tissue-specific targeting to the posterior segment and especially to the choroid and adjacent retina. Based on these findings, our long- term objective is to develop minimally invasive, targeted drug delivery methods that are superior to intravitreal injections, in order to enhance drug efficacy, while minimizing drug and injection-related side effects in treating CNV. In this study, we will test the hypothesis that suprachoroidal drug delivery offers a safe route of administration for sustained and effective therapy of posterior segment diseases such as CNV. The project has three specific aims: 1) Design and fabricate a minimally invasive microneedle device and determine its effect on targeted suprachoroidal delivery. 2) Determine the effect of drug physicochemical properties and sustained- release formulations on drug pharmacokinetics and biodistribution in the tissues of the back of the eye after suprachoroidal delivery. 3) Determine the efficacy and safety of suprachoroidal delivery of a small molecule drug and a macromolecule drug for sustained-release treatment of choroidal neovascularization. In addition to improving CNV therapy, the outcomes of this project will provide innovative targeted solutions for treating other posterior segment disorders including diabetic retinopathy, dry AMD, retinitis pigmentosa, and uveitis.