Cavitation mechanisms in ultrasound-enhanced permeability of ex vivo porcine skin

Abstract

Ultrasound-induced cavitation is known to enhance transdermal transport of drugs for local and systemic delivery. However, the specific cavitation mechanisms responsible are not well understood, and the physical location of permeability-enhancing cavitation is also unknown. The experiments reported here investigated the role of stable and inertial cavitation, both within the skin and at the dorsal skin surface, in ultrasound enhancement of skin permeability. Full-thickness porcine skin was hydrated with either air-saturated phosphate buffered saline (PBS) or vacuum-degassed PBS to localize cavitation activity within or outside the skin, respectively. Skin samples were sonicated for 30 minutes over a range of frequencies (0.41 and 2.0 MHz) and peak rarefactional pressure amplitudes (0-750 kPa) with a 20% duty cycle (1 s on, 4 s off). Cavitation activity was monitored using a 1.0 MHz unfocused, wideband passive cavitation detector (PCD). Changes in skin permeability were quantified by measuring the electrical resistance of skin every 10 seconds during insonation. Subharmonic acoustic emissions revealed a strong correlation with decreasing electrical resistance of skin when cavitation was isolated within the tissue, suggesting that stable cavitation within the skin plays a primary role in ultrasound-enhanced permeability over the frequencies investigated.