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Andrew J. McClellan, Emanuel Chang, Cintia S. De Paiva, William J. Farley, Stephen C. Pflugfelder; Biodegradable PLGA-Based Drug Delivery Systems for Modulating Ocular Surface Disease in a Murine Model. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3777.
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The rapid turn-over of the tear film makes continuous drug delivery to the ocular surface nearly impossible. Biodegradable polymers offer a unique solution to this problem by allowing the continuous elution of a drug without the danger of toxicity from either the drug or the polymer. The purpose of this study was to evaluate the potential for the use of poly-lactic-co-glycolic acid (PLGA) based polymers as drug delivery systems on the ocular surface.
A water-oil-water double emulsion method was used to encapsulate water-soluble compounds into PLGA-microshperes. Fluorescein-labeled albumin was encapsulated to evaluate the effect of changes to the synthesis protocol and molecular weight of polymers on protein elution in vitro and in vivo. Average size and variance was measured with confocal microscopy, and elution profiles were measured with spectrofluoroscopy. As proof of concept, doxycycline was loaded into the polymers and injected subconjunctivally. Staining with 70kDa Oregon green dextran (OGD)was used to assess corneal permeability of groups injected with normal saline(NS), NS plus 5 days of desiccating stress(5DS), sham-PLGA plus 5DS, or doxycycline-loaded-PLGA plus 5DS.
Using the parameters of our standard synthesis protocol encapsulation efficiency was close to 99%. PLGA-microparticle size was measured to be 4.6 µm±1.54 µm. Elution rate began at 2.5 µg/mg decreasing linearly by 0.08 µg/mg each day, over two weeks. It was found that particle size and elution profile could easily be manipulated with changes to the synthesis parameters. Subconjunctival injections doxycycline-loaded PLGA decreased corneal epithelial OGD permeability after 5DS (p<0.05).
PLGA microspheres provide an excellent vehicle for sustained drug delivery, capable of treating ocular surface disease in a way that has not yet been clinically utilized.
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