Undergraduate Research for Dose-Controllable Drug Delivery Implants

项目总结/文摘

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.