Abstract
Abstract: :
Purpose: To determine the in vitro transscleral permeability of antibiotics for posterior segment infection. Methods: Superior temporal sections of sclera were excised from moist–chamber human globes and mounted in a two–compartment perfusion chamber. Antibiotics (either fluorescent–labeled vancomycin, polymyxin B, or penicillin) were added to the donor hemichamber above the episcleral surface, while the receiver hemichamber below the choroidal surface was slowly perfused with BSS. A fraction collector was used to collect samples from the receiver chamber every hour, for a total of 24 hours. Concentration was measured using a fluorometer. From this data, the transscleral permeability (Ktrans, cm/sec) was calculated. Results: Ktrans for the transscleral diffusion of vancomycin (MW 1723.35 g/mol, n=12) was 1.46 ± 0.42 x 10–7 cm/s (mean +/– SEM). After a 24–hour experiment, 4.4 ± 1.2% of the total vancomycin diffused across the sclera, while 23.3 ± 2.4% remained in the scleral tissue and 19.3 ± 3.8% remained in the donor chamber. Ktrans for polymyxin B (MW 1800 g/mol, n=9) was 3.80 +/– 0.61 x 10–7 cm/s. After 24 hours, 17.2 ± 1.7% of the total polymyxin B diffused across the sclera, while 11.2 ± 1.8% remained in the scleral tissue and 14.2 ± 3.8% remained in the donor chamber. Ktrans for penicillin (MW 661.46 g/mol, n=10) was 2.10 +/– 0.41 x 10–6 cm/s. After 24 hours, 63.6 ± 10.2% of the total penicillin diffused across the sclera. Conclusions: Human sclera has been shown in previous studies to be permeable to a variety of compounds with different molecular weights. This study shows that, with respect to antibiotics, human sclera is more permeable to lower molecular–weight penicillin than to vancomycin or polymyxin B. In all cases, though, measurable concentrations of drug could be detected across the sclera. This series of experiments suggests that a local, non–invasive transscleral drug delivery method is feasible for using antibiotics to treat intraocular infections. These results also infer that other drugs can be applied transsclerally to treat a variety of diseases in the posterior segment.
Keywords: sclera • pharmacology • antibiotics/antifungals/antiparasitics