Cathodal iontophoresis was used to deliver insulin in 23 alloxan-diabetic, male, New Zealand white rabbits. Currents of 0.2–0.8 mA were used to deliver insulin from reservoirs containing insulin concentrations of 10–500 U/ml in aqueous solution. Regardless of the level of current used, within 1 h of turning the current on, blood glucose levels decreased and serum insulin concentrations increased. Moreover, in most cases, blood glucose levels continued to decrease and serum insulin concentrations continued to increase after the current was turned off, suggesting that iontophoresis could be used to accumulate insulin in the skin and subcutaneous tissues. The amount of insulin that was delivered by iontophoresis could be controlled by the level of current used up to 0.4 mA; increasing the current to 0.8 mA did not deliver more insulin. This may have been due to greater production of hydroxide ions at 0.8 mA, which competed with insulin to carry the current, thus slowing the movement of insulin. The amount of insulin delivered could also be controlled by the amount of insulin available for iontophoresis, i.e., as the insulin reservoir concentration increased, more insulin was delivered at the same current level. Finally, skin preparation was also important in controlling insulin delivery. To deliver enough insulin to reduce blood glucose levels, the stratum corneum had to be disrupted or removed by gentle scraping.

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