Ultrasound-mediated transdermal insulin delivery and glucose measurement using the cymbal array

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 ultrasonic transdermal delivery of insulin and glucose measurement 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 x 37 x 7 mm3 in size and weighed less than 22g. To evaluate the efficacy of the array as a practical insulin delivery and glucose measurement device, one in vitro and three in vivo experiments have been designed for this study. For in vitro experiment, human cadaver skin from skin bank were used while hyperglycemic rats and rabbits were used for in vivo experiments. Human skin was placed in a Franz diffusion cell and exposed to the ultrasound for an hour. The increased concentration of insulin in the receiver chamber of a Franz diffusion Cell was measured in a spectrophotometer. The concentration of insulin in the chamber after ultrasound exposure increased 10-fold. For an in vivo test, thirty Sprague Dawley rats were divided in six groups. Each animal was anesthetized with a combination of ketamine and xylazine. The abdominal area of the rats were shave and the array was placed on the surface of the shaved skin. With 5 minutes of ultrasound exposure (I sptp = 100 mW/cm2, 20% duty cycle), blood glucose level decreased 233.3 +/- 22.2 mg/dL in 90 minutes compared to the glucose level of untreated control groups. To explore the efficacy of the array in larger animal, sixteen New Zealand White rabbit experiments were performed in three groups: two controls and one ultrasound with insulin exposure. The rabbits were anesthetized and their thigh area was shaved for the exposure area. After one hour of ultrasound and insulin exposure, the glucose level was decrease to -132.6 +/- 35.7 mg/dL compared to the levels of glucose of control groups. For noninvasive glucose measurement, twelve Sprague Dawley rats were used. The array was placed on the shaved abdominal skin of the rats and the skin was exposed to ultrasound for twenty minutes. The device was removed and the electrochemical glucose sensor was placed on the skin. The glucose level was measured by the electrochemical sensor and compare to the results from a commercial glucose meter. The difference between two results was about 68.8 +/- 57.5 mg/dL. These results indicate the feasibility of the cymbal array for ultrasound enhanced transdermal insulin delivery and glucose measurement.