Permeability of Pure Enantiomers of Timolol Across SIRC Rabbit Corneal Cells
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abstract
The permeability characteristics of S- and R-isomers of timolol maleate across SIRC rabbit corneal cells in the presence and absence of benzalkonium chloride were evaluated. The barrier properties of the cell line were assessed by measuring transepithelial electrical resistance (TEER) and the permeability of a hydrophilic marker, mannitol. The permeability of S-timolol maleate across the SIRC layers was slightly higher than the reported value across the corneal membrane. There was no significant difference between the permeability of S- and R-isomers, indicating that there was no stereoselective transport across the cell line. The permeability of the low molecular weight isomers was greater than the permeability of mannitol suggesting that both paracellular and transcellular pathways contribute to the transport of these enantiomers across the cell line. The permeability of S- and R-isomers of timolol maleate and mannitol increased 2.8- and 5.2-times, respectively, in the presence of benzalkonium chloride. However, the cell layers showed a significant decrease in TEER after 2 h in the presence of 0.01% benzalkonium chloride. These findings suggest the possible use of the SIRC rabbit corneal cell line model to assess the permeability characteristics of enantiomers of timolol maleate.
