Exploitation of sub-micron cavitation nuclei to enhance ultrasound-mediated transdermal transport and penetration of vaccines.

Inertial cavitation mediated by ultrasound has been previously shown to enable skin permeabilisation for transdermal drug and vaccine delivery, by sequentially applying the ultrasound then the therapeutic in liquid form on the skin surface. Using a novel hydrogel dosage form, we demonstrate that the use of sub-micron gas-stabilising polymeric nanoparticles (nanocups) to sustain and promote cavitation activity during simultaneous application of both drug and vaccine results in a significant enhancement of both the dose and penetration of a model vaccine, Ovalbumin (OVA), to depths of 500μm into porcine skin. The nanocups themselves exceeded the penetration depth of the vaccine (up to 700μm) due to their small size and capacity to 'self-propel'.

Cavitation-enhanced delivery of insulin in agar and porcine models of human skin.

Ultrasound-assisted transdermal insulin delivery offers a less painful and less invasive alternative to subcutaneous insulin injections. However, ultrasound-based drug delivery, otherwise known as sonophoresis, is a highly variable phenomenon, in part dependent on cavitation. The aim of the current work is to investigate the role of cavitation in transdermal insulin delivery.

Exploitation of acoustic cavitation-induced microstreaming to enhance molecular transport.

Ultrasound (US) exposure of soft tissues, such as the skin, has been shown to increase permeability, enhancing the passage of drug molecules via passive processes such as diffusion. However, US regimes have not been exploited to enhance active convective transport of drug molecules from a donor layer, such as a gel, into another medium. A layered tissue-mimicking material (TMM) was used as a model for a drug donor layer and underlying soft tissue to test penetration of agents in response to a range of US parameters.