Ultrasound mediated transdermal in vivo transport of insulin with low profile cymbal arrays

Recent studies have shown that ultrasound mediated transdermal drug delivery offers a promising potential for noninvasive drug administration. The purpose of this study was to demonstrate ultrasound mediated transdermal delivery of insulin in vivo using rats with a novel, low profile two-by-two ultrasound array based on the cymbal transducer. As a practical device, the cymbal array (f = 20 kHz) was 37 /spl times/ 37 /spl times/ 7 mm/sup 3/ in size, weighed less than 22 grams and has previously demonstrated transdermal insulin delivery using ex vivo human skin. Twenty Sprague Dawley rats (350-450 g) were divided in four groups, two controls and two ultrasound exposure with five rats in each group. The rats were anesthetized, shaved and placed in the dorsal decubitus position with a 1 mm thick, water tight standoff (reservoir) which held the insulin or saline arranged between the rat's abdomen and the ultrasound array. The first group (named Control 1) used insulin in the reservoir with no ultrasound while the second group (Control 2) had saline in the reservoir with ultrasound operating at I/sub sptp/ = 100 mW/cm/sup 2/ for 60 minutes. For the experiments, the third group (Exposure 60) employed insulin with ultrasound exposure for 60 minutes (I/sub sptp/ = 100 mW/Cm/sup 2/), whereas the last group (Exposure 20) used insulin with ultrasound operating with a 20 minutes exposure to examine the effects of time (I/sub sptp/ = 100 mW/cm/sup 2/). At the beginning of the experiment and every 30 minutes for 90 minutes, 0.3 mL of blood was collected from the jugular vein to determine the blood glucose level (mg/dL) with a glucose monitoring system for diabetics. For comparison between the rats, the change in the blood glucose level was normalized to a baseline. The insulin reservoir was removed immediately after the array was turned off. For both Control 1 and 2, the glucose level remained constant at the normalized baseline level within a standard deviation of the mean for the entire 90 minutes. For the Exposure 60 group, the glucose level was found to decrease to -267.5 /spl plusmn/ 61.9 mg/dL in 60 minutes and decrease slightly after the ultrasound was removed. Moreover, to study the effects of ultrasound exposure time on insulin delivery, the 20 minutes group had essentially the same result as the 60 minutes exposure at a similar intensity which indicates that the expose time does not need to be as long as 60 minutes for delivery. The results indicate the feasibility of using a low cost, light weight cymbal array for enhanced transdermal insulin delivery using ultrasound.