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V Zderic, S Vaezy, RW Martin, JI Clark; Transcorneal Drug Delivery using Low-Frequency Ultrasound . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2319.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To evaluate the effectiveness of 20 kHz ultrasound in enhancing drug delivery through the cornea. Methods: The experiments were performed in albino rabbit corneas in vitro using a vertical diffusion cell. The donor compartment of the diffusion cell was filled with a drug solution and the receiver compartment was filled with a phosphate-buffered saline. Beta-blocker drugs of different lipophilicity (atenolol, carteolol, timolol, and betaxolol) were used. The cornea was exposed to the drug solution for 60 minutes in all experiments. Ultrasound was applied with the average intensity of 2 W/cm2 and exposure durations of 10, 30 and 60 minutes. The ultrasound transducer was positioned at 0.5 cm distance from the cornea in the donor compartment. Drug concentration in the samples taken from the receiver compartment was determined using an UV-visible spectrophotometer. The corneas were stained with hematoxylin and eosin, and examined by light microscopy. Results: A statistically significant difference between the treatment and control drug concentration was achieved after 10-30 minutes for all 4 drugs. After 60 min of ultrasound application, the drug concentration increased by 2.6 times for atenolol (p< 0.05), 2.8 times for carteolol (p< 0.01), 1.9 times for timolol (p< 0.001), and 4.4 times for betaxolol (p< 0.001), compared to the control concentration. The increase was highest for the most lipophilic drug, betaxolol. Histological analysis showed that ultrasound may produce epithelial disorganization and structural changes in the corneal stroma. Conclusion: We have demonstrated the potential use of ultrasound for the drug delivery into the eye. Further studies are needed to determine the optimal ultrasound parameters for a safe and effective treatment.
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