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K.G. Carrasquillo, S. Ray, I.K. Rigas, P. Calias, J.W. Miller, E.S. Gragoudas, A.P. Adamis; Transscleral Delivery of an Anti-VEGF Aptamer in a Rabbit Model . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4442.
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Purpose: To establish methods for the controlled delivery of bioactive anti-VEGF aptamer via the transscleral route. Methods: The anti-VEGF aptamer was encapsulated into PLGA (50/50) polymer microspheres and packed into a PDMS delivery device. Devices containing drug-loaded microspheres or blank microspheres, right and left eyes respectively, were placed on the temporal sclera of Dutch belted rabbits. One and two weeks following device placement, aptamer delivery and bioactivity were assessed via the inhibition of VEGF-induced blood-retinal barrier breakdown. Blood-retinal barrier breakdown was induced through the intravitreal injection of VEGF (1 µg/ml) and was quantified via the Evans blue method. Results: Blood-retinal barrier breakdown was potently induced by VEGF. Placement of PDMS devices loaded VEGF aptamer containing microspheres inhibited blood-retinal barrier. The inhibition was effective 1 and 2 weeks after device placement (P<0.05). Conclusions: In vivo transcleral delivery of a bioactive molecule has been demonstrated utilizing an anti-VEGF aptamer. By combining microsphere encapsulation with transcleral delivery, VEGF-induced retinal vascular permeability was decreased over a two-week period. These results represent a new delivery approach for anti-VEGF aptamers.
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