Biodegradable PLGA-Based Drug Delivery Systems for Modulating Ocular Surface Disease under Experimental Murine Dry Eye
|Emmanuel Chang#, Andrew J. McClellan#, William J. Farley, De-Quan Li, Stephen C. Pflugfelder and Cintia S. De Paiva*|
|Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA|
|#Both authors contributed equally|
|Corresponding Author :||Cintia S. de Paiva
Ocular Surface Center, Department of Ophthalmology
Cullen Eye Institute, Baylor College of Medicine
6565 Fannin Street, NC 205- Houston, TX 77030, USA
E-mail: [email protected]
|Received September 18, 2011; Accepted November 02, 2011; Published November 06, 2011|
|Citation: Chang E, McClellan AJ, Farley WJ, Li DQ, Pflugfelder SC, et al. (2011) Biodegradable PLGA-Based Drug Delivery Systems for Modulating Ocular Surface Disease under Experimental Murine Dry Eye. J Clinic Experiment Ophthalmol 2:191. doi:10.4172/2155-9570.1000191|
|Copyright: © 2011 Chang E, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
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Objective: Continuous drug delivery to the ocular surface remains difficult due to the rapid tear clearance of topically applied agents. The purpose of this study was to evaluate biodegradable and biocompatible drug delivery systems on the ocular surface using poly-lactic-co-glycolic acid (PLGA) based polymers.
Methods: Fluorescein-labeled albumin and doxycycline were individually encapsulated into a PLGA-based matrix using a water-oil-water double emulsion method. The drug elution rates for various microspheres were evaluated spectrofluorometrically. Particle size was measured using image analysis software. Subconjunctival injections of PLGA microspheres were used to evaluate safety and inflammatory response to the polymer in the murine model. Efficacy of the drug delivery system was evaluated by a single subconjunctival injection of PLGA-doxycycline (a broad metalloproteinase inhibitor) prior to induction of desiccating stress (DS) model in C57BL/6 mice for 5 days.
Results: PLGA-based microspheres successfully elute encapsulated drugs of interest continuously over controlled periods of time. Mean PLGA-based microparticle diameter was 4.6 µm ±1.54 µm. Drug elution rates and delivery times were easily modifiable by altering polymers and synthesis parameters. In vitro studies demonstrate successful continuous elution of encapsulated drugs for at least 2 weeks. In vivo testing of PLGA-doxycycline was efficacious in preventing DS-induced corneal barrier disruption with desiccating stress, similarly to topically applied doxycycline.
Conclusions: PLGA-based drug delivery systems are safe and non-inflammatory. They can be successfully used to treat ocular surface and corneal diseases by continuously delivering biopharmaceuticals of interest.