TRANSDERMAL IONTOPHORETIC DELIVERY OF INSULIN USING A PHOTOETCHED MICRODEVICE

In order to develop practical iontophoretic devices for insulin delive ry, five types of device, a square type, a square anode with a U-shape d inset cathode type device (2 divided type), and three types with a s quare anode, with, respectively, 4, 9 and 16 small square inset cathod es (4, 9 and 16 divided types), were fabricated by a photoetching tech nique, and their effectiveness was examined in vitro by measuring the permeability of 6-carboxyfluorescein (6-CF) through the excised abdomi nal skin of a nude mouse. All four divided types enhanced the penetrat ion rate of 6-CF more than 16-fold compared with passive diffusion. To test the transdermal iontophoretic delivery of insulin in normoglycem ic control and diabetic rats, we selected the 2 divided type device, s ince this pattern was the easiest to fabricate. A significant reductio n in blood glucose level (BGL) of 33% after 90 min of treatment, and a corresponding increase in immunoreactive insulin (IRI) concentration were observed in diabetic rats during cathodic direct current (DC) ion tophoresis (IF) at a constant voltage of 1.5 V. The effectiveness of p ulsed IP was also studied, but there was no significant difference bet ween DC and pulsed IP in the decrease of BGL. The level of current dur ing the initial 10 min was closely related to the hypoglycemic effect. These findings suggest that some cathodic reaction products may chang e the function of the stratum corneum or that these products may devel op a shunt pathway and enhance the transdermal delivery of aggregated insulin molecules. Iontophoresis-induced skin damage was also evaluate d by measuring impedance changes. It was shown that at constant-voltag e IP of 1.5 V, TP could be carried out for up to 60 min without any ma rked effects on the skin.