Enhanced transdermal delivery of pioglitazone hydrochloride via conductive hydrogel microneedles combined with iontophoresis

The conventional oral administration of pioglitazone for Type II diabetes management is frequently compromised by hepatic first-pass metabolism and associated systemic adverse effects, necessitating the development of enhanced transdermal delivery approaches. This study developed a transdermal drug delivery system combining conductive hydrogel microneedles and iontophoresis to improve the transdermal delivery of pioglitazone hydrochloride (PIO) and its therapeutic efficacy in the treatment of type II diabetes. The microneedles, fabricated using poly(methyl vinyl ether-<i>alt</i>-maleic anhydride) as the main matrix material, exhibited excellent conductivity, mechanical strength, and high drug loading capacity. In vitro permeation experiments demonstrated that, when combined with iontophoresis at a current intensity of 0.5 mA, the cumulative permeation of PIO reached 238.1 ± 27.14 μg/cm² within 48 h, significantly higher than that of the microneedle group alone. In a type II diabetic rat model, the microneedle-iontophoresis system displayed a significantly better hypoglycemic effect than the oral administration group, with a blood glucose reduction of 6.3 mmol/L on day 8, significantly higher than the 5.1 mmol/L reduction in the positive control group. Pharmacokinetic analysis indicated that the T_max, T_1/2, and mean residence time of the system were longer than those of oral administration, indicating sustained-release characteristics. Skin irritation tests revealed that the system caused only mild, transient skin irritation, with complete skin recovery within 24 h. In conclusion, conductive hydrogel microneedles combined with iontophoresis can effectively enhance PIO transdermal delivery, bioavailability, and therapeutic efficacy while also exhibiting good safety and potential clinical application value.