Pharmacokinetics of Suprachoroidal Delivering using Microneedles

使用微针进行脉络膜上递送的药代动力学

• 批准号: 9225211
• 负责人: Bryce Chiang
• 金额: $ 4.4万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9225211
• 关键词: Address; Adhesions; Adverse effects; Age related macular degeneration; Anatomy; Award; Biological Availability; Biomedical Engineering; Blindness; Bypass; Choroid; Clinical; Communication; Data; Deposition; Development; Diffusion; Disease; Dose; Drug Delivery Systems; Drug Kinetics; Drug Targeting; Engineering; Ensure; Event; Eye; Family suidae; Fellowship; Formulation; Frequencies; Goals; Healthcare; Healthcare Systems; Hour; Image; Inferior; Injectable; Injection of therapeutic agent; Institutes; Joints; Kinetics; Knowledge; Leadership; Learning; Liquid substance; Medical; Methods; Microspheres; Mind; Modeling; Motion; Movement; Needles; Ophthalmology; Optic Disk; Oryctolagus cuniculus; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Physicians; Positioning Attribute; Property; Regimen; Research; Retina; Role; Route; Scanning; Scientist; Sclera; Shapes; Techniques; Technology; Testing; Thick; Time; Tissues; Training; Travel; Ultrasonography; Visual impairment; Work; ciliary artery; combat; controlled release; design; histological specimens; in vivo; medical schools; new technology; novel; particle; prevent; public health relevance; reconstruction; skills; therapy development

 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.

 描述（由适用提供）：后部疾病，例如与年龄相关的黄斑变性，占视觉障碍和失明的1000万例，这对美国医疗保健系统造成了巨大燃烧。 We believe that the development of novel methods to deliver controlled-release formulas specifically to disseased tissues in the eye, while sparing non-diseased tissues, can be efficient, as well as simplifying the dosing regimen, of the Micron-sized needles, aka microneedles can be used to deliver drugs into the suprachoroidal space (SCS: a potential space between the choroid and sclera).该药物输送系统在治疗许多后段疾病方面可能是有利的，因为它（i）绕过眼部障碍而不会穿透视网膜，从而导致更高的生物利用度； （ii）提供与脉络膜相邻的药物，导致脉络膜浓度更高；和 （iii）防止药物扩散到眼睛的其他区域，从而限制副作用。由于SCS微针注射是一种相对的新技术，因此这项拟议的工作将进行基础研究，以确定使用微针注入SCS中的颗粒和流体载体的药代动力学。具体而言，我们建议（1）确定相关的解剖屏障，以限制流体在SC中的传播； （2）确定SCS膨胀的动力学，以及该动力学在SC中注入的颗粒沉积中的作用； （3）确定动力学一种SCS崩溃的机理，并验证SC塌陷会阻碍粒子运动。对SCS药代动力学的深入了解将使疗法和策略的持续发展，以治疗后部疾病。奖学金申请人试图成为一名成功且独立的物理科学家，专门研究眼科和工程技术，以打击视力丧失。为了实现这一目标，适用的将学会（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能力。该奖项开始时，该适用的将在埃默里医学院和佐治亚理工学院和埃默里医学院联合生物医学工程系的埃默里医学院和2年的研究生学习完成2年的医学培训。