2088977 Ultrasound-Enhanced Delivery of Anti-Inflammatory Ophthalmic Drugs

Abstract

s S63 Methods: In vitro experiments were performed in a standard diffusion cell setup utilizing excised corneas of New Zealand White rabbits. The corneas were exposed to a 0.02% topical solution of polyhexamethylene biguanide (PHMB), a compound used in the treatment of Acanthamoeba keratitis. PHMB has average molecular weight of 2400 g/mol and is a hydrophilic compound. Ultrasound was applied at frequency of 400 kHz and intensity of 0.8 W/cm2 for 5 min (since these parameters were found optimal in our previous studies with steroid drugs). Temperature was measured with a thin thermocouple in the proximity of the cornea during ultrasound application. After the experiment, amounts of the drug that penetrated through the cornea were determined using a spectrophotometer, and these quantities were utilized to find corneal permeability to PHMB. Histological studies were performed to determine changes in the cornea due to ultrasound application. Results: The concentration of PHMB in the receiver compartment of the diffusion cell was 2.85 60.87x10-5 % in sham-treated cases and 16.3265.99x10-5 % in ultrasoundtreated cases. The PHMB delivery increase through the cornea due to ultrasound application was 5.7 times. The corneal damage due to ultrasound application was limited to the surface layers of the corneal epithelium and was shown previously to recover within 90 min. The measured temperature increase during ultrasound application was 2 C. Conclusions: Our long-term goal is to develop an inexpensive, convenient, and minimally-invasive ultrasound method that can be applied in an outpatient clinic and eventually at home to facilitate delivery of medications into diseased eye tissues. 2088977 Ultrasound-Enhanced Delivery of AntiInflammatory Ophthalmic Drugs Marjan Nabili, Sankara Mahesh, Craig Geist, Vesna Zderic Biomedical Engineering, The George Washington University, Washington, DC, United States; Ophthalmology, The George Washington University, Washington, DC, United