Therapeutic ultrasound for improving the tropical corneal delivery of macromolecules

The goal of this project is to facilitate the delivery of topical drugs into the cornea and anterior segment of the eye using therapeutic ultrasound which could present a promising treatment for keratoconus and other corneal diseases. Each cornea is dissected and placed in a diffusion cell. smURFP-blue, a blue fluorescent chromophore, was used as the drug. The experimental groups of corneas were treated with 1 and 0.8 W/cm2 continuous ultrasound for 5 min at frequencies of 400 kHz and 600 kHz, respectively, then left in the diffusion cell for another 55 min. Fluorescence images of the fixed corneas were obtained to determine the relative amount of smURFP-blue that remained in the tissue. Safety of ultrasound application was tested by comparing the damage in the corneal layers. Spectroscopy measurements indicated no statistical difference in the presence of the chromophore in the receiver compartment in ultrasound- and sham-treatment groups. Preliminary results showed greater fluorescent intensity in the cornea when smURFP-blue is delivered with ultrasound compared to smURFP-blue added without ultrasound. The histology studies did not show any significant damage in ultrasound-treated corneas. This work may allow for the development of an inexpensive, clinically applicable, and minimally invasive ultrasound method for corneal drug delivery.