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E. S. Kim, L. Berglin, K. Morohoshi, D. H. Geroski, H. F. Edelhauser; In vitro Diffusion of Avastin (Bevacizumab) Across Human Sclera. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5988.
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To determine whether Avastin can diffuse across human sclera as a less invasive method of drug delivery.
Human donor sclera was placed in a perfusion chamber and 200µl (n=5) or 500µl (n=4) of Avastin (25 mg/ml) was placed on the episclera for 24 hours. Balanced Salt Solution (BSS) was used as a control on scleral tissue. Fractions of diffused perfusate were collected bihourly, and drug concentrations were measured using a sandwich ELISA. Histoimmunostaining of the sclera post-experiment was examined using confocal microscopy after 2, 5, 12, and 24 hrs of drug exposure. Drug wash out procedure was performed on 60µm lamellar sections following experimentation to determine drug distribution within the sclera.
A peak concentration of Avastin in the choroidal side of the sclera occurred at 10-12 hrs, followed by a decrease in concentration throughout a 24 hr period. Avastin reached peak scleral diffusion of 1.26 µg/ml at 10 hrs, and 0.920 µg/ml at 12 hrs after placing 200µl and 500µl on the scleral surface, respectively. Wash out studies show mean (±SD) concentration of 31.9 ± 12.3 ng/ml within each 60µm lamellar section of sclera. Confocal images display scleral uptake of the drug, while control samples showed little to no fluorescence.
From these results, Avastin shows potential to be delivered to the posterior eye transsclerally as a noninvasive method to treat AMD.
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