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N. Jiang, M. Prausnitz, H. Edelhauser, D. Geroski; Measurement and Prediction of Lateral Diffusion Within Human Sclera . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5391.
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Purpose: To examine the lateral diffusion profile of molecules within human sclera in vitro and develop a theoretical model for prediction of drug delivery kinetics and distribution. Methods: Strips of full–thickness sclera were excised from moist–chamber human globes obtained from the Georgia Eye Bank and suspended vertically in a glass vial, with the lower 3 mm of sclera dipped into a solution of 9.0e–5 M sulforhodamine (MW=558 Da). After carrying out triplicate experiments over exposure times of 4, 24, 48, 72 and 168 h, tissue samples were sectioned on a cryostat into 50 µm thick pieces, and the average sulforhodamine concentration in each set of 15 consecutive pieces was determined using spectrofluorimetry. A mathematical model of one–dimensional semi–infinite diffusion was also developed to predict the diffusion profiles and compared with the experimental data. In addition, rates of trans–scleral diffusion were also measured to determine the permeability of sulforhodamine across the sclera. Results: Experimental measurements showed that the concentration of sulforhodamine within the sclera depended significantly on both time and distance along the sclera. After just 4 h, sulforhodamine was seen to diffuse 4 mm along the sclera and to diffuse as far as 1 cm along the sclera after 1–week. Equilibrium experiments further showed a sclera–to–saline partition coefficient of 13.6, indicating significant binding of sulforhodamine to scleral tissue. These data were fitted to a theoretical model, which yielded an effective diffusion coefficient for lateral diffusion of sulforhodamine in sclera of 4.0e–6 cm2/s. Companion measurements of sulforhodamine diffusion across the sclera were characterized by an effective trans–scleral diffusion coefficient of 9.8e–7 cm2/s. Conclusions: Rates of lateral diffusion along the sclera can be experimentally measured and theoretically characterized. Comparison with trans–scleral diffusion indicated similar diffusion coefficients, although lateral diffusion was approximately four times faster. Based on an average human scleral surface area of 17 cm2, these data suggest that it would require up to 10 weeks for sulforhodamine to diffuse from a localized source throughout the sclera.
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