Ocular Drug Delivery using 20 kHz Ultrasound

摘要

The cornea is a major pathway for drug delivery to diseased eye structures. However, the corneal epithelium is sealed with tight junctions, and often less than 1% of applied drugs can penetrate through. We have investigated the application of 20 kHz ultrasound, at an average intensity of 2 W/cm~2, for enhancement of corneal permeability to glaucoma drugs of different lipophilicity (carteolol, timolol, and betaxolol). The experiments were performed in rabbit cornea in vitro using a diffusion cell. At an ultrasound exposure duration of 56 min, the permeability increased by 2.5 times for carteolol, 1.8 for timolol and 4.8 for betaxolol (p-value < 0.05). The permeability increase was usually accompanied by epithelial disorganization. Occasionally, structural changes in the corneal stroma were observed. The enhancement of permeability appeared to be a function of ultrasound exposure duration. The ultrasound and drug were also applied separately in order to distinguish immediate from long-term ultrasound effects. Data suggested that for lipophilic betaxolol ultrasound-induced convection was the dominant mechanism in enhancing drug penetration. For less lipophilic timolol and carteolol, permeability enhancement was likely caused by both convection and epithelial damage.