This project seeks to treat age related macular degeneration (AMD) by creating a platform for the sustained intra-ocular delivery of antibody-based therapeutic agents to inhibit vascular endothelial growth factor (VEGF). This interdisciplinary team will design and manufacture prototype nanoporous thin-film devices;establish drug loading techniques and drug release properties;and complete pre-clinical biocompatibility and functional testing in vitro and in animal eye models. Unlike other sustained release technologies, the proposed thin-film devices are functionally tunable to achieve zero-order drug release kinetics, attaining a flat drug release profile and a tight concentration range over several months. By sequestering drug in an underlying reservoir layer within the device, the drug can be protected from the external microenvironment. This ability to load and protect the drug is key for biologically-based therapies which often undergo rapid degradation and clearance from the eye. The device design proposed in this program will mitigate many challenges inherent in ocular drug delivery and provide an innovative approach to the delivery of ocular therapeutics.

Public Health Relevance

Progress in therapeutics for retinal diseases is closely linked to advances in ocular drug delivery. The intra-ocular drug delivery platform proposed here can enhance the administration and efficacy of ophthalmologic drugs for a variety of posterior eye diseases. We propose the use of an injectable nanoporous thin film device to provide drug release with zero-order kinetics over several months, for the delivery of both large molecule and biologic drugs.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY021574-02
Application #
8327712
Study Section
Gene and Drug Delivery Systems Study Section (GDD)
Program Officer
Shen, Grace L
Project Start
2011-09-01
Project End
2015-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
2
Fiscal Year
2012
Total Cost
$379,264
Indirect Cost
$129,264
Name
University of California San Francisco
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Bernards, Daniel A; Bhisitkul, Robert B; Wynn, Paula et al. (2013) Ocular biocompatibility and structural integrity of micro- and nanostructured poly(caprolactone) films. J Ocul Pharmacol Ther 29:249-57