Transdermal delivery of regular insulin to chronic diabetic rats: effect of skin preparation and electrical enhancement

Abstract

The efficacy of passive transdermal versus electrically-enhanced, or iontophoretic delivery of insulin was studied. The effect of skin pre-treatment on iontophoretic delivery of insulin was also investigated. Rectangular pulses of 0.25 mA/cm 2 current amplitude, 2 kHz frequency, and 50% duty cycle were used as anodal stimulation for electrically enhanced transdermal delivery of insulin. Twenty (20) BB/Wor chronic diabetic adult male rats were shaved 48 h prior to the study, and some experimental groups had hair stubble removed with a depilatory lotion. The iontophoretic drug-containing electrode was filled with 3 ml of porcine regular insulin (100 IU/ml) which had been adjusted to an acidic pH of 3.68 using 0.1 M HCl. The iontophoretic electrodes were then adhered to the abdomen of the alert rat. Results of the iontophoretic procedure were quantified by monitoring changes in blood glucose levels. When insulin was placed on the shaved skin, blood glucose levels fell in the chronic diabetic rat. In general, glucose levels fell more quickly and more profoundly using an iontophoretic enhancement of transdermal insulin delivery. However, some skin preparations facilitated movement of insulin more efficiently. The most profound effect of lowered blood glucose occurred when a depilatory lotion was used on the day of the study in conjunction with iontophoresis, where blood glucose levels fell by 61% after 1 h of iontophoretic treatment. Results indicate that insulin was delivered passively at therapeutic levels when the skin had been treated with the depilatory lotion on the same day as the study, as measured through a reduction in blood glucose levels of 29% after 1 h of passive delivery. When the depilatory lotion was used 24 h prior to iontophoresis, blood glucose remained near initial blood glucose levels. In the groups that did not have the depilatory lotion applied, blood glucose levels fell by 8% after 1 h of iontophoretic insulin delivery. The experimental evidence indicates a substantial increase in the penetration of insulin with the same-day application of a depilatory lotion in conjunction with iontophoretic enhancement.