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（由申请人提供）：眼后段疾病，例如年龄相关性黄斑变性，导致超过 1000 万例视力障碍和失明病例，给美国医疗保健系统带来了沉重负担。我们相信，开发新方法将控释制剂专门递送至眼部患病组织，同时保留非患病组织，可以有效地治疗许多眼后段疾病，并简化给药方案。微米大小的针，又名微针，可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）。这种药物输送系统在治疗许多眼后段疾病方面具有优势，因为它（i）绕过眼部屏障而不穿透视网膜，从而产生更高的生物利用度； (ii) 将药物输送到脉络膜附近，导致脉络膜视网膜中的药物浓度更高；和 (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，因此这项拟议工作将进行基础研究，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。具体来说，我们建议 (1) 确定限制 SCS 中液体扩散的相关解剖学障碍； (2) 确定 SCS 膨胀的动力学，以及该动力学在注入 SCS 的颗粒沉积中的作用； (3)确定SCS塌陷的动力学机制，并验证SCS塌陷阻止粒子运动。对 SCS 药代动力学的深入了解将有助于持续开发治疗后段疾病的疗法和策略。奖学金申请人寻求成为一名成功且独立的医师科学家，专门从事眼科和工程技术以对抗视力丧失。为了实现这一目标，申请人将学习（i）确定临床需求并评估提出的解决方案，（ii）规划和执行研究计划，以及（iii）培养有效的沟通和领导技能。在该奖项开始时，申请人将在埃默里医学院完成 2 年的医学培训，并在佐治亚理工学院和埃默里医学院联合生物医学工程系完成 2 年的研究生学习。