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.

Public Health Relevance

Posterior segment ocular diseases, such as age-related macular degeneration, account for >10 million cases of blindness and visual impairment in the U.S. Hollow microneedle technology enables targeted ocular drug delivery of sustained-release formulations into the suprachoroidal space for the treatment of a wide range of posterior segment diseases. The goal of this project is to study the pharmacokinetics of suprachoroidal delivery using microneedles. A better understanding of pharmacokinetics is critical to the development of this targeted drug delivery system.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30EY025154-03
Application #
9225211
Study Section
Special Emphasis Panel (ZRG1-F15-P (20)L)
Program Officer
Agarwal, Neeraj
Project Start
2015-02-01
Project End
2019-01-31
Budget Start
2017-02-01
Budget End
2018-01-31
Support Year
3
Fiscal Year
2017
Total Cost
$43,576
Indirect Cost
Name
Emory University
Department
Biomedical Engineering
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Chiang, Bryce; Wang, Ke; Ethier, C Ross et al. (2017) Clearance Kinetics and Clearance Routes of Molecules From the Suprachoroidal Space After Microneedle Injection. Invest Ophthalmol Vis Sci 58:545-554
Chiang, Bryce; Venugopal, Nitin; Grossniklaus, Hans E et al. (2017) Thickness and Closure Kinetics of the Suprachoroidal Space Following Microneedle Injection of Liquid Formulations. Invest Ophthalmol Vis Sci 58:555-564
Chiang, B; Kim, Y C; Doty, A C et al. (2016) Sustained reduction of intraocular pressure by supraciliary delivery of brimonidine-loaded poly(lactic acid) microspheres for the treatment of glaucoma. J Control Release 228:48-57
Chiang, Bryce; Venugopal, Nitin; Edelhauser, Henry F et al. (2016) Distribution of particles, small molecules and polymeric formulation excipients in the suprachoroidal space after microneedle injection. Exp Eye Res 153:101-109
Kim, Yoo Chun; Chiang, Bryce; Wu, Xianggen et al. (2014) Ocular delivery of macromolecules. J Control Release 190:172-81