(210a) Rapid Skin Permeabilization By The Simultaneous Application Of Dual-Frequency Ultrasound

Transdermal drug delivery is an attractive delivery route because of the ease of access of the skin.  However, the skin acts as an effective barrier. Therefore, large molecules must be delivered with needles, which are painful and can increase the transmission of infectious diseases. Low frequency ultrasound has previously been studied for its ability to painlessly increase the permeability of the skin. Despite this work, ultrasound has not yet attained wide clinical use due to limitations on the resulting permeability. We hypothesized that skin permeability can be enhanced by coupling a high-frequency ultrasound signal to the existing low-frequency treatment. Aluminum foil pitting experiments, along with in vitro tests performed with porcine skin, tested the simultaneous application of two distinct frequencies ranging from 20 kHz to 3 MHz to examine their effect on the formation of localized transport regions (LTRs) within the skin. These experiments demonstrated that skin permeability and resulting LTR size both increased as a result of dual-frequency treatment compared to low-frequency treatment alone.  Glucose (180 Da) and inulin (5000 Da) transdermal flux experiments further confirmed these results by demonstrating enhanced delivery through and into the dual-frequency-treated skin. This methodology can be a viable option for transdermal drug delivery.