Sonophoresis cavitational

Tezel, A., and S. Mitragotri. 2003. Interactions of inertial cavitation bubbles with stratum corneum lipid bilayers during low-frequency sonophoresis. Biophys J 85 3502. 

Another popular physical enhancement method that has routes in physical therapy and sports rehabilitation clinics is sonophoresis. Sonophoresis involves the use of ultrasound as a source of disrupting intercellular lipid structures in the stratum corneum [39,40].The sound waves produced by the device induce cavitation of the lipids found within the stratum corneum, which then opens channels and allows the chemical compound to easily penetrate the skin. This is a safe and reversible process that has received much attention in the literature and by pharmaceutical companies. 

Ultrasound (or sonophoresis) is a technology more traditionally associated with the fields of physiotherapy, sports medicine, and medical imaging rather than transdermal dmg delivery. Compared to physiotherapy, where high-frequency energy (1 MHz) is used, in transdermal dmg delivery low-frequency energy (20 kHz region) is applied across the skin. Cavitation, the acoustically induced formation and oscillation of gas bubbles formed because of the mechanical energy supplied, is the most probable... 

The use of ultrasound (US) to enhance percutaneous absorption (so-called sonophoresis or phonophoresis) has been studied over many years, and is the basis of US propagation and US effects on tissue, and the use of US in transdermal delivery have been reviewed in detail. The proposed mechanisms by which US enhances skin penetration include cavitation, thermal effects and mechanical perturbation of the SC that is, US acts on the barrier function of the membrane. ... 

Ultrasound can be applied either in a continuous or a pulsed mode. A pulsed mode of ultrasound application is used many times because it reduces the severity of adverse side effects of ultrasound, such as thermal effects. However, pulsed application of ultrasound may have a significant effect on the efficacy of sonophoresis. As will be discussed later, cavitational effects, which play a crucial role in sonophoresis,... 

Mortimer, Trollope, and Roy " performed sonophoresis of oxygen across frog skin in vitro. They found that the sonophoretic enhancement of transdermal oxygen transport depends on ultrasound intensity, rather than pressure amplitude. Based on this observation, they hypothesized that cavitation cannot be responsible for sonophoresis. They hypothesized that... 

In the first set of experiments, the known effect of static pressure on cavitation was utilized. It is known that cavitation in fluids and porous media can be suppressed at high pressures. This effect is believed to occur due to the dissolution or collapse of the gaseous nuclei under the influence of pressure. Sonophoresis experiments were performed using skin compressed at 30 atm (between two smooth glass plates soaked in water placed in a compression press for two hours prior to sonophoresis experiments). They found that while application of ultrasound (IMHz, 2W/cm continuous) enhances estradiol permeability of the normal human epidermis by 13-fold, the corresponding enhancement for compressed skin is only about 1.75-fold. 

Since cavitational effects in fluids vary inversely with ultrasound frequency, it is likely that cavitational effects should play an even more important role in low-frequency sonophoresis. Tachibana et al. hypothesized that application of low-frequency ultrasound results into acoustic streaming in the hair follicles and sweat ducts of the skin, thus leading to enhanced transdermal transport. Mitragotri et al. hypohesized that transdermal transport during low-frequency sonophoresis occurs across the keratinocytes rather than hair follicles. They provided the following hypothesis for the higher efficacy of low-frequency sonophoresis. 

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