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IK Rigas, E Ahmed, J Ambati, KG Carrasquillo, ES Gragoudas, JW Miller, AP Adamis; Pulsatile Transscleral Drug Delivery . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2301.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:To study the kinetics of the pulsatile transscleral drug delivery using labeled IgG. Methods:A small biocompatible plastic (Polypropylene) chamber was attached to the bare scleral surface of anesthetized pigmented rabbits with the help of cyanoacrylate glue and loaded with 15ug of FITC-conjugated rabbit IgG. Transscleral diffusion of IgG into the ocular tissues was quantified at 15, 24, 48, 72 and 120hrs. Tissue samples were collected prior to sacrifice, and FITC-IgG concentration was determined by fluorophotometry. Choroid and retina along with other tissues were assayed. All the results were corrected for tissue autofluorescence by comparison to the fellow eye. Scleral flat mounts were examined under a fluorescent microscope and the transscleral diffusion pattern was visualized. Results:The IgG concentration in the choroid started to increase at 15hrs (3.761.7ug/ml, P=0.008) and peaked at 24hrs (14.786.96ug/ml, P=0.009). Statistically significant elevations in choroidal IgG concentration were observed out to 5days (3.7350.9ug/ml, P=0.008). IgG concentration in the retina started to increase after 15hrs and reached significant levels at 24hrs (2.241ug/ml, P=0.009) and 48hrs (2.1720.97ug/ml, P=0.0019), n=5 at all times. At 24hrs, approximately 5% (4.841.72) of the total drug placed on the sclera was detected within the combined choroid and retina. Examination of scleral flat mounts under a fluorescent microscope revealed maximum lateral diffusion within the sclera at 48hrs, with significant residual scleral FITC-IgG fluorescence visible at the site of the chamber even after 5days. Conclusion:An experimental animal model for studying the kinetics of the pulsatile transscleral drug delivery has been developed. These data demonstrate that the pulsatile transscleral delivery of IgG can result in potentially therapeutic levels in the choroid and retina with the sclera itself acting as a potential drug reservoir for IgG.
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