Noninvasive ultrasonic transdermal insulin delivery in rabbits using the light weight cymbal array

The purpose of this study was to demonstrate US transdermal delivery of insulin in vivo using rabbits with a novel, low profile two-by-two US array based on the cymbal transducer. As a practical device, the cymbal array (f=20 kHz) was 37×37×7 mm³ in size and weighed less than 22g. With a similar intensity (I_sptp=100 mW/cm², 20% duty cycle), our goal was to determine if the same effect could be achieved with rabbits. Fourteen New Zealand White rabbit (2.7-3.4 kg) experiments were performed in three groups: two controls and one US with insulin exposure. The first group (control 1) had insulin placed in the reservoir with no US while the second group (control 2) had saline in the reservoir with US operating at I_sptp=100 mW/cm² for 60 minutes. The third group (US-Insulin) was subjected to insulin with US exposure for 60 minutes (I_sptp=100 mW/cm²). At the commencement of the experiment, 0.3 mL of blood was collected from the ear vein to determine the blood glucose level (mg/dL) using a blood glucose monitoring system. The insulin reservoir was removed with the array after the US was turned off at 60 minutes exposure. For both control 1 and 2, the blood glucose level showed an increase at 15 and 30 minutes and remained at approximately +50 mg/dL. For the US-Insulin group, the glucose level was found to decrease -132.6±35.7 mg/dL in 60 minutes. After the US and insulin were removed, the blood glucose level of US-Insulin group continued to decrease to -208.1±29 mg/dL. These results indicate the feasibility of using a low cost, light weight Cymbal array for enhanced transdermal insulin delivery using US.