Ocular drug delivery using 20-kHz ultrasound.

The cornea is a major pathway for drug delivery to diseased eye structures. We have investigated the application of 1-s bursts of 20-kHz ultrasound, at I(SAPA) of 14 W/cm(2) (I(SATA) of 2 W/cm(2)), for enhancement of corneal permeability to glaucoma drugs of different lipophilicity (atenolol, carteolol, timolol and betaxolol). The permeability of rabbit cornea increased by 2.6 times for atenolol, 2.8 for carteolol, 1.9 for timolol and 4.4 times for betaxolol (all p-values < 0.05), after 60 min of ultrasound (US) exposure in vitro. The differences between the treatment and control experiments were statistically significant after 10 to 30 min of US exposure for all four drugs. US application appeared to produce epithelial disorganization and structural changes in the corneal stroma. Further studies are needed to determine the optimal US parameters for a safe and effective treatment.