Transscleral diffusion of ethacrynic acid and sodium fluorescein

Transscleral drug delivery is an effective method for treatment of eye diseases in posterior segment. Therefore, we investigated transscleral permeability of ethacrynic acid (ECA), a potential drug for treating glaucoma. To determine the ex vivo permeability of ECA across the sclera, we quantified the diffusion coefficients of two molecules, ECA and sodium fluorescein, in fresh porcine sclera mounted in a two-chamber diffusion apparatus. All experiments were conducted with phosphate-buffered solution (PBS) at 4/spl deg/C for a period ranging from 2 to 14 hours. The concentrations of ECA and sodium fluorescein were measured at room temperature (25/spl deg/C) with UV and fluorescence spectrophotometers, respectively. The results showed that the permeability of ECA (303 Da) was 4.21/spl plusmn/0.82/spl times/10/sup -5/ cm/sec (n=9), whereas the permeability of sodium fluorescein (376 Da) was 1.06/spl plusmn/0.88/spl times/10/sup -6/ cm/sec (n=12). These results suggest that the sclera tissue is more permeable to ECA than sodium fluorescein.