抄録
The poor oral bioavailability (BA) of clinically effective peptides requires that these agents be administrated primarily by parenteral routes, Non-invasive systems for peptide delivery are therefore very attractive and have long been studied. Iontophoresis is one such system where macromolecules are delivered with high potency. Pulse depolarization systems are iontophoretic systems that depolarize the skin (i. e., neutralize the charge stored in the skin capacitance) after each pulse of an applied current. In this study, we evaluated a pulse depolarization iontophoretic system (PDP-IP) as a peptide delivery system. The evaluation involved measuring the BA of a model peptide, salmon calcitonin (sCT), at various dosages and currents using either transdermal or transbuccal administration in dogs. The BA in transbuccal iontophoresis against intramuscular administration, with a constant transport current of 0.2 mA for 1 hour, was about 10 times higher than the BA in transdermal iontophoresis (1% vs 10%). In transbuccal iontophoresis, with a constant voltage of 8 V, there was a liner relationship between dosage and AUC of sCT serum concentration. Furthermore, electrically induced transport of sCT depended on the total transport current(mA × min). The difference in electrical characteristics between skin and buccal mucosa may be the reason for the difference in iontophoretic peptide delivery between these two membranes : buccal resistance is lower than skin resistance, although buccal impedance is similar to skin impedance. Other possible factors include site differences in enzymatic activity and non-specific binding. PDP-IP effectively enhanced the peptide delivery in both transbuccal and transdermal administration. However, the enhancement in macromolecular drug delivery was greater for the transbuccal iontophoresis (faster delivery rate and higher amount of drug absorption) than for the transdermal iontophoresis. Although further experiments are needed to clarify possible local irritation, PDP-IP is very attractive as a transbuccai delivery system for macromolecular drugs.
