Purpose: Application of low-frequency ultrasound has been shown to increase skin permeability, thereby facilitating delivery of macromolecules (low-frequency sonophoresis). In this study, we sought to determine the dependence of low-frequency sonophoresis on ultrasound frequency, intensity and energy density.
Methods: Pig skin was exposed to low-frequency ultrasound over a range of ultrasound frequency and intensity conditions. The degree of skin permeabilization was measured using its conductivity. Imaging experiments were also carried out to visualize the transport pathways created by ultrasound.
Results: The data showed that for each frequency (in the range of 19.6-93.4 kHz), there exists a threshold intensity below which no detectable conductivity enhancement was observed. The threshold intensity increased with frequency. It is feasible to achieve the desired conductivity (permeability) enhancement regardless of the choice of frequency, although the necessary energy density is higher at higher frequencies. Low frequencies (approximately 20 kHz) induced localized transport compared to a more dispersed effect seen with higher frequencies (approximately 58.9 kHz).
Conclusions: This study provides a quantitative understanding of the effects of low-frequency ultrasound on skin permeability.