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Pamela Ko, Jonathan Moreno, Paulin Wahjudi, Rueben Merideth, Ricardo Carvalho; Transscleral diffusion and comparative ex vivo permeability of dorzolamide in canine, equine, porcine and rabbit sclera. Invest. Ophthalmol. Vis. Sci. 2014;55(13):447.
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© ARVO (1962-2015); The Authors (2016-present)
To characterize the ex vivo transscleral diffusion of dorzolamide and compare its diffusion and permeability profile across the canine, equine, porcine and rabbit sclera.
The sclera was harvested from fresh canine, equine, porcine and rabbit globes. The samples were mounted between the donor and receptor compartments onto the curved surface of water-jacketed Franz cells, comprising a 5-mm diffusion window and maintained at 37oC. Balanced salt solution was the media utilized in the receptor chamber. Solutions containing 2mg/ml and 20mg/ml of dorzolamide (n=3) were dispensed into the donor compartments and samples were collected from the receptor sites at 15,30,45,60,90,120,180,240,300,360 minutes and 24 hours. The sclera and residual solutions in the donor chambers were collected at the end of the run for analysis. The collected samples were analyzed by previously developed sensitive high-performance liquid chromatography (HPLC) assay for dorzolamide. The trans-scleral flux(F), permeability coefficients (Papp) and effective diffusion coefficient (Deff) of dorzolamide were calculated. Permeability parameters were determined and compared with ANOVA statistical analysis (p<0.05).
Preliminary HPLC analysis permeability parameters of four species were calculated. The trans-scleral flux through rabbit sclera showed an approximate twofold higher than the equine sclera at 20 mg/ml concentration of dorzolamide (656 ug/cm2 hr of rabbit and 364 ug/cm2 hr for equine sclera). Differences in thickness of sclera produced differences in the permeability coefficient. Rabbit had the thinnest sclera with the highest Papp (9.11E-06 cm/s) followed by porcine, horse and canine. Considering the effective diffusion coefficient (Deff) was affected by the scleral thickness, porcine had the highest values at both 2 and 20 mg/ml of dorzolamide concentration.
The data obtained from this ex-vivo experiment indicated the interspecies scleral differences and antiglaucoma drug profile affect the outcomes of trans-scleral delivery. Barring from the scleral composition differences, this experiment proved that human antiglaucoma drugs are able to permeate the animal sclera. This suggests a possible use of trans-scleral route as an alternative drug delivery method for translational research and development, but also the treatment of retinal diseases in veterinary ophthalmology.
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