Noninvasive Transdermal Insulin Delivery Using Piston-Shaped PZT Transducers: In vivo Rabbits Evaluation

Abstract

Noninvasive transdermal insulin delivery is investigated in this paper utilizing ultrasound transducers in order to improve the quality of life of Type 1 diabetic patients. This alternative technique is intended to replace the long-term dependence on multiple subcutaneous insulin injections. Different piston-shaped ultrasound transducers operating in the frequency range 100 – 1000 kHz were housed using silicone adhesive which included a reservoir to hold insulin during in vivo transdermal delivery. Twenty five local rabbits were divided into five groups and anesthetized using a combination of Ketamine hydrochloride and Xylazine to produce temporarily diabetic rabbit models during the period of experiments. Consisting of five rabbits in each experimental group, the control group (G0) did not receive ultrasound while exposure groups (G1-G4) received ultrasound for only ten minutes. Sweep driving mode of operation over a range of frequencies was applied to each exposure group with different frequency ranges. The swept frequency ranges were 100-200, 200-400, 400-650, and 650-1000 kHz for exposure groups G1, G2, G3, and G4, respectively. Initially, blood glucose level of rabbits (n = 25) was 157.2 ± 17.4 (mg/dl) and increased to 302.4 ± 78.1 mg/dl in one-hour period for the control group. In contrast, exposure groups (G1-G4) showed variable behaviors of glucose level reductions depending on driving frequencies with lowest value of 100.6 ± 17.9 (mg/dl) (G1) after one-hour from the starting of the ten minute exposure period. Compared to the control group, exposure groups showed reduction of blood glucose levels by 21.6%, 10.8%, 3.4%, and 3.7% for exposure groups G1, G2, G3, and G4, respectively, after twenty minutes from exposure period. The reduction of blood glucose levels continued till the end of the one-hour measurement period with maximum recorded reductions, compared to the control group, were 66.7%, 35.9%, 39.5% and 45% for groups G1, G2, G3, and G4, respectively. Ultrasound piston PZT transducers were found to facilitate insulin delivery across the skin of rabbits regardless of the driving frequency in the tested range from 100 to 1000 kHz. However, driving frequencies from 100 to 200 kHz were found to be the best facilitator of insulin delivery compared to other tested frequencies.