Pharmacokinetics of Suprachoroidal Delivering using Microneedles

 描述（由申请人提供）：后段疾病，如年龄相关性黄斑变性，造成超过1000万例视力损害和失明，这对美国医疗保健系统构成了重大负担。我们相信，开发将控释制剂特异性地递送至眼睛中的患病组织而保留非患病组织的新方法可以是有效的，并且简化了治疗许多后段疾病的给药方案。微针可以用于将药物输送到脉络膜上腔（SCS：脉络膜和巩膜之间的潜在空间）。这种药物递送系统在治疗许多后段疾病中可以是有利的，因为它（i）绕过眼部屏障而不穿透视网膜，导致更高的生物利用度;（ii）邻近脉络膜递送药物，导致脉络膜视网膜中更高的浓度;和（iii）在视网膜中递送药物，导致视网膜中更高的浓度。 (iii)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，因此本研究将开展基础研究，以确定使用微针注射到SCS中的颗粒和液体载体的药代动力学。具体而言，我们建议（1）确定限制SCS中液体扩散的相关解剖屏障;（2）确定SCS扩张的动力学，以及该动力学在SCS中注入的颗粒沉积中的作用;以及（3）确定SCS塌陷的动力学机制，并验证SCS塌陷阻止颗粒运动。对SCS药代动力学的深入了解将使治疗后段疾病的疗法和策略的持续发展成为可能。奖学金申请人寻求成为一个成功的和独立的医生科学家专门从事眼科和工程技术，以打击视力丧失。为了实现这一目标，申请人将学习（i）确定临床需求并评估拟议的解决方案，（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。在此奖项开始时，申请人将在埃默里医学院完成2年的医学培训，并在格鲁吉亚理工学院和埃默里医学院的联合生物医学工程系完成2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.