TRANSDERMAL IONTOPHORETIC DELIVERY AND DEGRADATION OF VASOPRESSIN ACROSS HUMAN CADAVER SKIN

Transdermal iontophoretic transport and degradation of a peptide, vasopressin, across human cadaver skin, was investigated. Modified Valia-Chien cells were supplied with 0.5 mA/cm(2) current density via silver/silver chloride electrodes from a Scepter(R) power supply. Vasopressin (0.25 mg/ml) spiked with [H-3]vasopressin was transported across skin with anode in donor. Samples were analyzed by HPLC using a radio-chromatography detector. Degradation of vasopressin in contact with intact skin and in skin homogenates was also studied. Greater degradation was observed in receptor where the peptide was in contact with the dermal side of the skin. The cumulative amounts of intact vasopressin permeated during 8 h of iontophoretic transport was 15.37 (+/-5.31; n = 3) mu g/cm(2), which corresponds to only about 1% permeation. Of the total radioactivity permeated, only about 40% was intact vasopressin by 12 h. Several degradation peaks could be seen in the chromatogram. No intact vasopressin was found to permeate under passive conditions. The enzymatic activity of cadaver skin is likely to be less than that expected in an in vivo drug delivery situation. Therefore, delivery to patients would be even less than that predicted by this study.