Evaluation of Pulsed Current Iontophoresis for Enhancing the Transdermal Absorption of the Osteoporosis Drug Teriparatide

This study aimed to evaluate the feasibility and safety of pulsed-current iontophoresis (IP) for the transdermal delivery of teriparatide, a therapeutic peptide for osteoporosis. Female rats were subjected to in vivo iontophoretic administration under constant or pulsed-current conditions. Serum teriparatide concentrations, skin irritation scores, and transepidermal water loss (TEWL) were assessed. After 2 h of IP, serum teriparatide concentrations reached 53.3 ± 4.0 pg/mL with pulsed current and 48.8 ± 12.6 pg/mL with constant current, confirming successful transdermal absorption of teriparatide (≈4 kDa) into systemic circulation. Skin irritation was significantly reduced under pulsed-current conditions, as indicated by lower erythema, edema, and TEWL values, despite identical total current exposure. These results suggest that intermittent current application during pulsed-current IP alleviates local electrical stress through partial depolarization and may provide a delivery efficiency comparable to that of constant direct current IP while improving tolerability. Overall, pulsed-current IP enables noninvasive and effective systemic delivery of peptide drugs with minimized skin irritation, representing a promising alternative to injection-based administration for macromolecular therapeutics.