Therapeutic ultrasound for enhanced transcorneal macromolecule delivery

Previous experiments demonstrated that ultrasound exposure at 400-600 kHz can increase transcorneal drug delivery of sodium-fluorescein. Our study aims to determine if these same methods can enhance the delivery of fluorescently labeled FITC-dextran macromolecules of similar molecular weights to clinically relevant drugs. Dissected corneas of adult rabbits were placed in a diffusion cell between a donor compartment filled with a solution of FITC-dextran macromolecules diluted with phosphate-buffered saline (PBS) to 1 mg/ml and a receiver compartment filled with PBS. Each cornea was exposed to the drug solution for 60 minutes, with the experimental group receiving 5 min of continuous ultrasound or 10 min of pulsed ultrasound at 50% duty cycle at the beginning of treatment. Unfocused circular ultrasound transducers were operated at 0.5 –1 W/cm2 intensity and at 600 kHz frequency. Macromolecule delivery was quantified by the fluorescence intensity detected in the receiver compartment. The greatest increase in transcorneal drug delivery seen was 1.2 times (p < 0.05) with the application of pulsed ultrasound at 0.5 W/cm2 and 600 kHz for 10 min with 40 kDa macromolecules. Gross observation of corneas after experiments demonstrated no significant damage. Ongoing microscopy and thermal-modeling studies aim to characterize any ultrasound-induced damage.