Iontophoretic transdermal absorption of insulin and calcitonin in rats with newly-devised switching technique and addition of urea

Abstract

The effect of urea and reversing polarity of electrodes (switching technique) in iontophoresis was investigated in order to get a better transdermal absorption of peptide drugs, insulin and calcitonin, and to reduce dermal irritation caused by the iontophoresis. Two cells with an electrode were set on the hair-removed abdominal skin of diabetic or oophorectomized rats. After putting peptide solution into the anode side or both of the cells, an electric current with pulsed rectangular wave form (4 kHz, 50% duty) was passed through the skin for 2 h at 0.075 mA cm −2 (insulin) and for 50 min or 2 h at 0.015 mA cm −2 (calcitonin). Absorption of insulin and calcitonin was estimated from the reduction of glucose and calcium levels in the plasma of the rats, respectively. When the polarity of electrodes was reversed at intervals of 20 min for insulin and 25 min for calcitonin, absorption of the drug was effectively enhanced. The addition of urea to the insulin solution together with the switching technique brought about a remarkably facilitated absorption of insulin. Moreover, comparison of the skin conditions between switching and non-switching experiments suggested that irritation of skin could be reduced by employment of the switching iontophoresis.