Undergraduate Research for Dose-Controllable Drug Delivery Implants

项目摘要/摘要 这项研究的总体目标是改进糖尿病等慢性后眼病的治疗 黄斑水肿(DME)、黄斑水肿(ME)或慢性非感染性后葡萄膜炎(NU)和减少侧 皮质类固醇缓释引起的影响。目前对慢性支气管炎患者的护理标准 DME/ME/NU是玻璃体内注射缓释皮质类固醇植入物(Ozurdex)。然而，最近的一次 NEI资助的一项研究发现，缓释皮质类固醇治疗导致更多的局部副作用 与全身抗炎治疗相比，如异常高眼压、青光眼和 白内障。我们推测，这个问题是因为在不需要的时候无法调整剂量。这个 从Ozurdex释放的玻璃体或视网膜中的药物浓度在前30天很高，这可能会导致 高眼压的直接不良后果。此外，临床研究显示，高达 68%的患者在玻璃体内注射皮质类固醇两次以上后出现白内障，这通常 需要动手术。 我们的中心假设是我们的新型地塞米松植入物--剂量可以精确到 由激光控制--可减少玻璃体内注射后因剂量无法控制而产生的副作用 给药，延长治疗效果。利用我们在眼睛生物机制方面的专业知识， 在生物医学纳米技术和临床研究方面，我们最近开发了一种可生物降解的光活化植入物 这可以在玻璃体内注射，并由激光通过眼睛的晶状体触发以释放药物。这种药 通过改变激光参数，如功率和持续时间，可以精确和轻松地控制剂量。我们的 该方法将克服该领域的重大障碍，提供由激光精确控制的理想剂量 没有安全方面的考虑。 具体目标1的重点是完成地塞米松植入物的开发，并研究长期的 长期药物体外释放动力学研究。具体目标2侧重于确定不同给药方式的效果 关于减少体外副作用，包括每日给药，光激活植入物，和奥祖德。 特异性目标3将确定植入物的体内疗效和减少的副作用，与奥祖德相比 葡萄膜炎兔模型。在该项目成功完成时，预期成果包括确定 光激活植入物潜在改变慢性后眼护理标准的可行性 药物递送。此外，该项目与本科研究相结合，将加强研究 为本科生创造良好的学习环境，并对学校产生实质性的影响。

PROJECT SUMMARY/ABSTRACT The overall goal of this research is to improve the treatment of chronic posterior eye diseases such as diabetic macular edema (DME), macular edema (ME) or chronic non-infectious posterior uveitis (NU) and reduce side effects caused by sustained-release of corticosteroids. Current standard of care for long-lasting conditions of DME/ME/NU is intravitreal injections of sustained-release corticosteroid implants (Ozurdex). However, a recent NEI-funded study found that sustained-release corticosteroid treatments caused more local side effects compared to systemic anti-inflammation treatment, such as abnormally high eye pressure, glaucoma, and cataracts. We postulate that this problem is because of the inability to adjust the dosage when not needed. The drug concentration in the vitreous or retina released from Ozurdex is high in the first 30 days, which can result in immediate adverse consequence of high intraocular pressure. In addition, clinical studies revealed that up to 68% of patients experience cataract after more than 2 intravitreal corticosteroid implant injections, which often requires surgery. Our central hypothesis is that our novel version of dexamethasone implant – where the dose can be precisely controlled by laser – would reduce the side effects due to uncontrollable dosage after intravitreal administration, and extend therapeutic efficacy. Leveraging our expertise in ocular biological mechanisms, biomedical nanotechnology, and clinical studies, we recently developed a biodegradable light-activated implant that can be intravitreally injected and triggered by laser through the lens of the eye for drug release. The drug dosage can be precisely and easily controlled by varying laser parameters, such as power and duration. Our approach will overcome significant barriers in the field by delivering desirable dose precisely controlled by laser without safety concerns. The focus of Specific Aim 1 is to complete the development of a dexamethasone implant and investigate long- term drug release kinetics in vitro. Specific Aim 2 focuses on defining effect of different drug delivery methods on reducing side effects in vitro, including daily administration, the light-activated implant, and Ozurdex. Specific Aim 3 will determine in vivo efficacy and reduced side effects of the implant compared to Ozurdex in a uveitis rabbit model. At the successful completion of this project, expected outcomes include identifying feasibility of the light-activated implants to potentially change the standard of care for chronic posterior eye drug delivery. In addition, the project integrated with undergraduate research will strengthen the research environment for undergraduate students and have a substantial effect on the institution.