Frequency and thermal effects on the enhancement of transdermal transport by sonophoresis.

The aims of this work were: (i) to examine the role of ultrasound (US) frequency and intensity on the transport of glucose and mannitol across porcine skin in vitro, (ii) to quantify the energy delivered to the skin during application of low-frequency sonophoresis, and (iii) to 'deconvolute' the thermal effect, induced by US application to the skin, to the enhanced permeability of the cutaneous barrier. Low- (20 kHz) and high-frequency (10 MHz) sonophoresis were first compared. Only low frequency US resulted in significantly increased permeation. Low-frequency, US-induced enhancement of mannitol transport was symmetric; that is, mannitol flux was the same when 'delivered' or 'extracted' from a donor solution (in both cases, the US probe was present on the surface side of the skin). Calorimetry was used to quantify the US energy delivered by the sonicator. Subsequently, the US-enhanced transdermal transport of mannitol, during which a significant (and US intensity-dependent) temperature increase occurred, was compared to that provoked, in the absence of sonophoresis, by a comparable thermal effect. Only 25% of this enhancement was attributable to the increased temperature induced by US. It follows that another mechanism, most probably cavitation, is principally responsible for the lowered skin barrier function observed.