In-vivo evaluation of ultrasound transducers for noninvasive transdermal delivery of insulin using temporarily hyperglycemic rabbits and mice

Abstract

A noninvasive transdermal delivery of insulin, using piston-shaped PZT ultrasound transducers, was suggested to reduce regular pain and suffering of type 1 diabetic patients. This alternative technique is intended to replace the long-term dependence on multiple subcutaneous insulin injections. Ten rabbits and ten mice were divided equally into four groups (two control groups and two exposure groups). The animals were anesthetized using a combination of Ketamine hydrochloride and Xylazine to produce temporarily diabetic animal models during the periods of the experiments. Animals in control groups did not receive ultrasound while animals in exposure groups received ultrasound mediated delivery of insulin for 5 and 10 minutes for mice and rabbits, respectively, during the continuous driving of the transducers. Sweep driving frequency signals were assigned to each exposure group with frequency range from 100 to 200kHz. The signals were amplified to drive 30.0 mm diameter piston-shaped PZT transducers attached to the shaved skin of each exposed anesthetized animal. Custom made housing was used to create a reservoir to trap insulin between the face of the transducer and the exposed shaved abdomen areas of the animals during the delivery period. Blood glucose levels were measured depending on blood samples from the veins of the tails of the mice and the veins of the ears of the rabbits. These measurements were achieved using blood glucose meter every ten minutes for an hour starting from the delivery period. Over the recording period of 60 minutes, reduction of blood glucose levels compared to control groups were 67% and 50% for rabbits and mice, respectively. Ultrasound piston PZT transducers in the mid range frequency (100 to 200 kHz) were found feasible in transdermal insulin delivery in vivo using temporarily hyperglycemic rabbits and mice models.