Purpose: Ultrasound has been shown to enhance, by up to 10 times, the corneal permeability to different compounds such as beta-blockers and fluorescein. Here, we report on our investigation of the mechanisms of ultrasound-enhanced drug delivery through the cornea using light and electron microscopy.
Methods: Enhancement of permeability for a hydrophilic compound, sodium fluorescein, in rabbit cornea in vitro was achieved using ultrasound at a frequency of 880 kHz and intensities of 0.19-0.56 W/cm2 with an exposure duration of 5 minutes. Light and electron microscopy (transmission and scanning) were used to observe ultrasound-induced structural changes in the cornea.
Results: The permeability increased by 2.1, 2.5, and 4.2 times when ultrasound was applied at 0.19, 0.34, and 0.56 W/cm2, respectively (P<0.05). The surface cells of corneal epithelium exposed to ultrasound appeared swollen and lighter in color (indications of membrane rupture) as compared with the control cells. Some of the surface epithelial cells were absent. The cells in the inner layers of the epithelium were occasionally lighter in color. Also, holes 3-10 microm in diameter were observed on the epithelial surface. No structural changes were observed in the stroma.
Conclusion: Ultrasound enhancement of drug delivery through the cornea appears to result from minor structural alterations in the epithelium. Careful investigation of the recovery of cornea structure and barrier function after the ultrasound application, in vivo, is needed.