Pharmacokinetics of Suprachoroidal Delivering using Microneedles

 描述(申请人提供)：后部疾病，如老年性黄斑变性，占视力障碍和失明病例的1000万例，给美国医疗体系带来了巨大的负担。我们相信，开发新的方法，在保留非病变组织的同时，将控释制剂专门输送到眼睛内的病变组织，可以有效地治疗许多眼后节疾病，并简化给药方案。微米大小的针，又名微针，可以用来将药物输送到脉络膜上腔(SCS：脉络膜和巩膜之间的潜在间隙)。这种药物输送系统在许多后节疾病的治疗中可能是有利的，因为它(I)绕过眼球屏障而不穿透视网膜，从而产生更高的生物利用度；(Ii)在脉络膜附近输送药物，导致脉络膜视网膜中的浓度更高；以及 (3)防止药物扩散到眼睛的其他区域，限制副作用。由于SCS微针注射是一项相对较新的技术，这项拟议的工作将开展基础研究，以确定使用微针注入SCS的颗粒和流体载体的药代动力学。具体地说，我们建议(1)确定限制流体在SCS中扩散的相关解剖屏障；(2)确定SCS膨胀的动力学，以及该动力学在注入SCS中的粒子沉积中的作用；以及(3)确定SCS崩溃的动力学和机制，并验证SCS崩溃阻止粒子运动。对SCS药代动力学的深入了解将使治疗后节疾病的治疗方法和策略继续发展。奖学金申请者希望成为一名成功的独立内科科学家，专门从事治疗视力丧失的眼科和工程技术。为了实现这一目标，申请者将学习(I)识别临床需求和评估建议的解决方案，(Ii)计划和执行研究计划，以及(Iii)发展有效的沟通和领导技能。在该奖项开始时，申请者将在埃默里医学院完成两年的医学培训，并在佐治亚理工学院和埃默里医学院的联合生物医学工程系完成两年的研究生学习。

 DESCRIPTION (provided by applicant): Posterior segment diseases, such as age-related macular degeneration, account for >10 million cases of visual impairment and blindness, representing a significant burden on the U.S. healthcare system. We believe that the development of novel methods to deliver controlled-release formulations specifically to diseased tissues in the eye, while sparing non-diseased tissues, can be efficacious, as well as simplifying the dosing regimen, of the treatment of many posterior segment diseases. Micron-sized needles, aka microneedles can be used to deliver drugs into the suprachoroidal space (SCS: a potential space between the choroid and sclera). This drug delivery system can be advantageous in the treatment of many posterior segment diseases because it (i) bypasses ocular barriers without penetrating through the retina, resulting in higher bioavailability; (ii) delivers drugs adjacent to the choroid, resulting in higher concentrations in the chorioretina; and (iii) prevents diffusion of drugs to other regions of the eye, limiting side effects. Because SCS microneedle injections are a relatively new technology, this proposed work will carry out basic studies to determine the pharmacokinetics of particles and fluid carrier injected into the SCS using a microneedle. Specifically, we propose to (1) Identify relevant anatomical barriers that limit the spread of fluid in the SCS; (2) Determine the kinetics of SCS expansion, and the role of this kinetics in the deposition of particles injected in the SCS; and (3) Determine the kinetics an mechanism of SCS collapse, and verify that SCS collapse arrests particle motion. In-depth knowledge on SCS pharmacokinetics will enable the continued development of therapies and strategies to treat posterior segment diseases. The fellowship applicant seeks to become a successful and independent physician scientist specializing in ophthalmology and engineering technologies to combat vision loss. To reach this goal, the applicant will learn to (i) identify clinical needs and evaluate proposed solutions, (ii) plan and execute a research plan, and (iii) develop effective communication and leadership skills. At the start of this award, the applicant will have completed 2 years of medical training at the Emory School of Medicine and 2 years of graduate study in the joint biomedical engineering department of the Georgia Institute of Technology and the Emory School of Medicine.