Experimental demonstration of the existence of highly permeable localize transport regions in low-frequency sonophoresis

Recent advances in low-frequency sonophoresis have focused on the existence of hypothesized localized transport regions (LTRs). However, there has been no actual experimental demonstration that the hypothesized LTRs are, in fact, localized regions of high permeability. Through a series of low-frequency sonophoresis experiments conducted with full-thickness pig skin, in the presence of the surfactant sodium lauryl sulfate (SLS), in which we have separately measured the transport of calcein through the LTRs, which have areas ranging from 10 to 40 mm(2), and the surrounding regions of the skin (the non-LTRs) by means of a novel masking technique, we demonstrate that the calcein permeability through the LTRs is approximately 80-fold higher than the calcein permeability through the non-LTRs, suggesting that the LTRs are structurally perturbed to a greater extent than the non-LTRs from the exposure to the ultrasound/SLS system. In addition, we propose basic models to predict the total skin transdermal permeability from the transdermal permeabilities of the LTRs and the non-LTRs, and then compare the predictions to the experimental data obtained from the masking experiments. We also demonstrate that both the LTRs and the non-LTRs exhibit significant decreases in skin electrical resistivity relative to untreated skin (similar to5000-fold and similar to170-fold, respectively), suggesting the existence of two levels of significant skin structural perturbation due to ultrasound exposure in the presence of SLS. Finally, an analysis of the porosity/tortuosity ratio (epsilon/tau) values suggests that trans-cellular transdermal transport pathways are present within the highly permeable, and highly structurally perturbed, LTRs. (C) 2004 Wiley-Liss, Inc. and the American-Pharmacists Association.