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Pamela Peidrienne Ko, Jonathan Moreno, Robert Brito, Monica Vargas Dougherty, Ruebuen Merideth, Ricardo Carvalho; Comparative ex-vivo trans-scleral diffusion permeability of dexamethasone sodium phosphate in equine, porcine and rabbit scleras. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4136.
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© ARVO (1962-2015); The Authors (2016-present)
To characterize the ex vivo trans-scleral diffusion of dexamethasome sodium phosphate and compare its diffusion and permeability profile across the equine, porcine and rabbit scleras.
The scleras were harvested from fresh equine, porcine and rabbit globes. The samples were mounted between the donor and the receptor compartments onto the curved surface of water-jacketed Franz cells, comprising a 5-mm diffusion window and maintained at 37° C. Balanced salt solution was the media utilized in the receptor chamber. Solutions containing 10 and 100 mg/mL of dexamethasone sodium phosphate (Dex. SP.) (n=10 per concentration) were dispensed into the donor compartments and samples were collected from the receptor sites at 30,60,90,120,180,240,300,360 minutes. The sclera and residual solutions in the donor chambers were collected at the end of the run. The collected samples were analyzed by an UV-Vis spectrophotometer. The trans-scleral flux (F), permeability coefficient (Papp) and effective diffusion coefficient (Deff) of Dex. SP. were calculated. Permeability parameters were determined and compared with ANOVA statistical analysis (p<0.05).
Preliminary spectrophotometery analysis of dexamethasone SP. was carried out to calculate the cumulative amount recovery (microgram) over time and permeability parameters of three species were calculated. The equine flux at 100 mg/mL concentration had a higher average recovery rate than the 10 mg/mL concentration. It was the opposite in the porcine flux of the two concentration study. Rabbit sclera had reached drug diffusion saturation time fastest and equine was the slowest. It suggested a potential scleral anatomical compositional difference among species. The permeability coefficient values of two concentrations were similar within the same species (i.e. 100 mg/mL vs. 10 mg/mL in porcine).
We have shown that a model of water-soluble steroid anti-inflammatory drug is able to permeate the sclera in other species such as equine, porcine and rabbit animal models. The data obtained from this ex-vivo experiment demonstrated interspecies difference pertaining to the drug diffusion across the scleras. This suggests a possible use of trans-scleral route as an alternative drug delivery method for translational research and development, but also for the treatment of retinal diseases in veterinary ophthalmology.
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