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

Abstract

The purpose of this study was to demonstrate the feasibility of ultrasound (US)-mediated transdermal delivery of insulin in vivo using rats with a novel, low profile two-by-two US array based on the "cymbal" (due to its unique shape) transducer. As a practical device, the cymbal array (f = 20 kHz) was 37 x 37 x 7 mm in size, and weighed less than 22 g. A total of 20 Sprague-Dawley rats (350 to 450 g) were divided into four groups, two controls and two US exposure, with five rats in each group. The rats were anesthetized and shaved; a water-tight standoff reservoir, which held the insulin or saline, was sealed against the rat's abdomen and the US array. At the beginning of the experiment and every 30 min for 90 min, 0.3 mL of blood was collected from the jugular vein to determine the blood glucose level (mg/dL). For comparison 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 with no US and the second control group had saline in the reservoir with US operating at I(SPTP) = 100 mW/cm(2) for 60 min. For the experiments, the third group employed insulin with US exposure for 60 min (I(SPTP) = 100 mW/cm(2)), whereas the last group used insulin with US operating with a 20-min exposure (I(SPTP) = 100 mW/cm(2)) to examine the effects of time on delivery. For the 60-min US exposure group, the glucose level was found to decrease from the baseline to -267.5 +/- 61.9 mg/dL in 1 h. Moreover, to study the effects of US exposure time on insulin delivery, the 20-min group had essentially the same result as the 60-min exposure at a similar intensity, which indicates that the expose time does not need to be as long for delivery.