Assessment of the microvascular effect of insulin using transdermal iontophoresis: optimizing drug delivery in JOURNAL OF VASCULAR RESEARCH, vol 48, Suppl. 1, Poster Session II/2, pp 127-127

• Transdermal delivery by iontophoresis has been used previously to study the vascular effects of insulin in the cutaneous microcirculation. Although a vasodilatory effect of iontophoretically applied insulin has been shown, the observed increases in perfusion, as measured using laser Doppler flowmetry, are modest, possibly since delivered doses are limited due to the electrochemical properties of the molecule, and the relatively low permeability of the skin. Ethanol, urea and depilatory agents have previously been used to enhance transport of substances during iontophoresis. In this pilot study in 8 healthy volunteers, we aimed to investigate the effect of insulin on skin perfusion, as measured by laser-Doppler flowmetry. We tested various strategies that could possibly enhance the delivery of insulin to the skin using iontophoresis, including the use of an insulin analog (insulin aspart), pretreatment of the skin with ethanol and depilatory cream and using 50%/50% mixtures of insulin/ethanol and insulin/urea. Although a slight increase in skin perfusion was found in most subjects with iontophoresis of regular insulin using a single 10-minute current pulse of 0.02 mA (12 mC, N=4), this effect was not significant. Neither of the two pretreatment methods affected this effect. However, when using 9 x 20sec current pulses of 0.2 mA (36 mC, N=4), and when the drugs were mixed with ethanol in a 50%/50% fraction , a 15- to 17-fold increase in perfusion was found for insulin aspart (p=0.04). Iontophoresis of a control substance (50%/50% ethanol/sodium chloride) did not have any effect on skin perfusion (p=0.32). Similarly, iontophoresis of a mixture of urea and insulin aspart yielded a 14-fold increase in perfusion (p=0.03), while a non significant increase in perfusion was found when urea was mixed with regular insulin (p=0.08) and no change at all with sodium chloride (control, p=0.27). These results indicate that iontophoretic transport of insulin may be enhanced by using mixtures of insulin with ethanol or urea, which may facilitate studies that use iontophoresis to study the vascular effects of insulin in the cutaneous microcirculation. Further studies, for instance using microdialysis, are required to directly measure the delivered dose of insulin during iontophoresis under different conditions.

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