Feasibility of a closed-loop controlled noninvasive ultrasonic glucose sensing and insulin delivery system

Use of needles for multiple injections of drugs, such as insulin for diabetes, can be painful. As a result, prescribed drug noncompliance can results in severe medical complications. In previous studies, ultrasound mediated transdermal drug delivery has shown a promising potential as a method for noninvasive drug administration. Yet for prospective human application, a milestone to a practical clinical device of this research requires that the efficacy of the cymbal array be demonstrated on animals larger than rats and rabbits. Larger and possessing a blood volume similar to humans, pig is an appropriate animal model for further experimentation in evaluating the practicability of this ultrasound device. Six Yorkshire pigs (100 - 140 lbs) were divided into two groups. As the control (n = 3), the first group did not receive any ultrasound exposure with the insulin. The second group (n = 3) was treated with ultrasound and insulin at 20 kHz with an I_sptp = 100 mW/cm² at a 20% duty cycle for 60 minutes. With the pigs in lateral recumbency after anesthesia, the ultrasound transducer with insulin was placed on the axillary area of the pig. At the beginning and every 15 minutes up to 90 minutes, the blood glucose level was determined using a glucose monitoring system. To compare the results of individual animals, the change of blood glucose level was normalized to each animal's initial glucose value at the start of the experiment. Although each animal had a different initial glucose level, the mean and standard error for the six animals was 146 ± 13 mg/dl (Figure 1). For the control group, the blood glucose level increased to 31 ± 21 mg/dl compared to the initial baseline over the 90 minute experiment. However for the ultrasound with insulin treated group, the glucose level decreased to -72 ± 5 mg/dl at 60 minutes (p < 0.05) and continued to decreased to -91 ± 23 mg/dl in 90 minutes (p < 0.05). Results demonstrate a promising pre-clinical outcome for the low profile cymbal array to be used for ultrasound enhanced in vivo insulin transport using an animal with a similar size and weight to a human. The cymbal array has potential as a practical ultrasound system for noninvasive transdermal insulin delivery for diabetes management.