An in vivo investigation of the rabbit skin responses to transdermal iontophoresis

To optimize the benefits of transdermal iontophoresis, it is necessary to develop a suitable animal model that would allow for extensive assessments of the biological effects associated with electro-transport. Rabbit skin responses to iontophoresis treatments were evaluated by visual scoring and by non-invasive bioengineering parameters and compared with available human data. In the current density range 0.1–1.0 mA/cm² applied for 1 h using 0.9% w/v NaCl and 0.5 mA/cm² for up to 4 h, no significant irritation was observed. 2 mA/cm² applied through an area of 1 cm² for 1 h resulted in slight erythema at both active electrode sites but without significant changes in transepidermal water loss (TEWL) and laser Doppler velocimetry (LDV). A value of 4 mA/cm² under similar conditions caused moderate erythema at the anode and cathode with TEWL and LDV being significantly elevated at both sites; 1 mA/cm² current applied for 4 h, caused moderate erythema at both anode and cathode; and 1 mA/cm² applied for 1 h caused no irritation when the area of exposure was increased from 1 to 4.5 cm². When significant irritation and barrier impairment occurred, the erythema was resolved within 24 h with barrier recovery complete 3–5 days post-treatment. Rabbit skin thus shows promise as an acceptable model for iontophoresis experiments.