Short ultrasound exposure times for noninvasive insulin delivery in rats using the lightweight cymbal array

Abstract

The purpose of this study is to demonstrate the feasibility of using short ultrasound exposure times to noninvasively deliver insulin with a lightweight (<22 g), low-profile (37 x 37 x 7 mm3) cymbal array (f = 20 kHz). Using hyperglycemic rats, previous experiments using the array demonstrated that blood glucose would decrease approximately 250 mg/dl from 60 and 20 minutes of pulsed ultrasound exposure for transdermal insulin delivery. Using a similar intensity (Isptp = 100 mW/cm2, 20% duty cycle), the goal was to determine if the same effect can be achieved with only 5 minutes of ultrasound exposure. For these experiments, 20 Sprague Dawley rats were anesthetized and shaved, and a 1-mm watertight standoff reservoir that held the insulin or saline was placed between the rat's abdomen and the ultrasound array. At the beginning of the experiment and every 30 minutes, 0.3 ml of blood was collected from the jugular vein to determine the blood glucose level (milligrams per deciliter) for a total of 90 minutes. For comparison purposes between the rats, the change in the glucose level for each rat was normalized to a baseline (i.e., 0 mg/dl). The first control group used insulin in the reservoir without any ultrasound. The second control group had saline in the reservoir with ultrasound operating at Isptp = 100 mW/cm2 for 60 minutes. For the noncontrol experiments, the third group used insulin with ultrasound exposure for 10 minutes. The last group used insulin with ultrasound operating with a 5-minute exposure to examine the effects of using short ultrasound exposure times on delivery. For the 10- and 5-minute ultrasound exposure groups, the glucose level was found to decrease from the baseline to -174.6 +/- 67.2 and -200.4 +/- 43.4 mg/dl measured after 1 hour, respectively. These results indicated that ultrasound exposure times do not need to be long to deliver a clinically significant insulin dose to reduce a high blood glucose level.