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 #
5R01EY021574-04
Application #
8719113
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
2014-09-01
Budget End
2015-08-31
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Kim, Jean; Kudisch, Max; Mudumba, Sri et al. (2016) Biocompatibility and Pharmacokinetic Analysis of an Intracameral Polycaprolactone Drug Delivery Implant for Glaucoma. Invest Ophthalmol Vis Sci 57:4341-6
Lance, Kevin D; Bernards, Daniel A; Ciaccio, Natalie A et al. (2016) In vivo and in vitro sustained release of ranibizumab from a nanoporous thin-film device. Drug Deliv Transl Res 6:771-780
Schlesinger, Erica; Johengen, Daniel; Luecke, Ellen et al. (2016) A Tunable, Biodegradable, Thin-Film Polymer Device as a Long-Acting Implant Delivering Tenofovir Alafenamide Fumarate for HIV Pre-exposure Prophylaxis. Pharm Res 33:1649-56
Lance, Kevin D; Good, Samuel D; Mendes, Thaís S et al. (2015) In Vitro and In Vivo Sustained Zero-Order Delivery of Rapamycin (Sirolimus) From a Biodegradable Intraocular Device. Invest Ophthalmol Vis Sci 56:7331-7
Kim, Jean; Schlesinger, Erica B; Desai, Tejal A (2015) Nanostructured materials for ocular delivery: nanodesign for enhanced bioadhesion, transepithelial permeability and sustained delivery. Ther Deliv 6:1365-76
Schlesinger, Erica; Ciaccio, Natalie; Desai, Tejal A (2015) Polycaprolactone thin-film drug delivery systems: Empirical and predictive models for device design. Mater Sci Eng C Mater Biol Appl 57:232-9
Wade, Jennifer S; Desai, Tejal A (2014) Planar microdevices enhance transport of large molecular weight molecules across retinal pigment epithelial cells. Biomed Microdevices 16:629-38
Schweicher, Julien; Desai, Tejal A (2014) Facile Synthesis of Robust Free-Standing TiO2 Nanotubular Membranes for Biofiltration Applications. J Appl Electrochem 44:411-418
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
Kam, Kimberly R; Desai, Tejal A (2013) Nano- and microfabrication for overcoming drug delivery challenges. J Mater Chem B Mater Biol Med 1:1878-1884

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