9F-4 Rectangular Cymbal Arrays for Ultrasonic Transdermal Insulin Delivery

Abstract

Studies have shown that ultrasound mediated transdermal drug delivery offers a promising potential for needle-less insulin delivery for diabetes treatment. Arrays of cymbal transducers have been shown to be effective in delivering therapeutic levels of insulin to decrease hyperglycemic glucose levels in rats, rabbits and pigs. To improve delivery efficiency of the cymbal arrays, an increase in the spatial intensity field without increasing the size the device or Isptp was desired. A 3 times 1 rectangular cymbal array was designed for this purpose. Rectangular cymbals maximized packing density and allowed the flexural cap resonance and the ceramic length mode resonance frequencies to be designed closer in frequency. Bringing the cap and ceramic resonances closer together increased the transmitting power and improved the electrical efficiency. By using higher order modes excited in the cap while operating at the first ceramic resonance frequency, the intensity spatial area was increased compared to the circular array. With a similar intensity (I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">sptp</sub> ap 50 mW/cm ), our goal was to determine if the 3 times 1 rectangular cymbal array could perform significantly better than the 3 times 3 circular array for blood glucose reduction in hyperglycemic rabbits. Nine New Zealand White rabbit (ap 4.0 kg) experiments were performed in three groups: control (n = 3) and ultrasound exposure with the 3 times 3 circular cymbal array (n = 3) or 3 times 1 rectangular cymbal array (n = 3). The rabbits were anesthetized and their thigh area was shaved for the exposure. A water tight reservoir which held the insulin was fastened between the rabbit's thigh and the ultrasound arrays. At the beginning of the experiment and every 15 minutes for 90 minutes, 0.3 ml of blood was collected from the ear vein to determine the glucose level (mg/dl) using a glucose monitoring system. For comparison between individual rabbits, the change in the blood glucose level was normalized to their initial baseline value. For the control group, the glucose level increased (i.e. more hyperglycemic) to maximum of +80.0 plusmn 28.8 mg/dl over the 90 minute experiment. Using the 3 times 3 circular array, the blood glucose level decreased to -146.7 plusmn 17.8 mg/dl at 90 minutes. However, in comparison using the 3 times 1 rectangular cymbal array, the blood glucose decreased faster and to level of -200.8 plusmn 5.9 mg/dl after 90 minutes for 25% improvement. These results indicated the potential of the rectangular cymbal array as an advanced device for portable drug delivery by decreasing the power consumed and increasing the insulin delivery rate.