Heterogeneity in Skin Treated with Low-Frequency Ultrasound

Recent experimental evidence using colored, fluorescent permeants suggests that skin treated with low-frequency sonophoresis (LFS) is perturbed in a heterogeneous manner. Macroscopic and microscopic visualization studies, topical penetration studies, transdermal permeability studies, and skin electrical resistivity measurements have shown that discrete domains, referred to as localized transport regions (LTRs), which are formed during LFS treatment of the skin, possess greatly reduced barrier properties, and therefore exhibit increased permeant skin penetration, compared to the surrounding regions of LFS-treated skin. The transformation of LTR formation from a heterogeneous to a homogeneous phenomenon has the potential benefit of increasing the maximum level of transdermal permeability or of reducing the area of skin required to deliver a desired dose of drug transdermally. Future studies, aimed at elucidating both the mechanisms of LTR formation and the limits of nondamaging formation of LTRs in the skin, are required to incorporate these proposed improvements to enhance the efficacy and practical utility of low-frequency sonophoresis.