Sonophoresis

In heat-stripped stratum oorneum exposed to US, convection plays a key role and the effeotive pore radius produoed in the skin is much larger than that in full-thickness skin. 

The definitive role that oavitation plays in the enhancing mechanism has been described and predicted by using suitable mathematical models, whioh have also been employed to evaluate three modes of bubble cavitation (namely shock-wave emission, microjet penetration and miorojet impact) on the stratum oorneum. Both microjets and spherical collapses were found to be potentially responsible for the enhancing effect [117]. 

---

Mitragotri S, Kost J. Low-frequency sonophoresis—a review. Adv Drug Delivery Rev 2004 56 589-601. 

Sonophoresis is defined as the transport of drugs through intact skin under the influence of an ultrasound. Ultrasound at various frequencies in the range of 20 kHz to 16 MHz has been used to enhance skin permeability [1-3]. This chapter attempts to present sonophoresis, experimental variables, possible mechanisms of action, and clinical applications. 

Mitragotri, S., and J. Kost. 2004. Low-frequency sonophoresis A review. Adv Drug Deliv Rev 56,... 

Mitragotri, S., D. Blanckschtein, and R. Langer. 1996. Transdermal drug delivery using low-frequency sonophoresis. Pharm Res 13 411. 

Bommannan, D., et al. 1992. Sonophoresis. I. The use of high-frequency ultrasound to enhance transdermal drug delivery. Pharm Res 9 559. 

Tezel, A., A. Sens, and S. Mitragotri 2003. A theoretical description of transdermal transport of hydrophilic solutes induced by low-frequency sonophoresis. J Pharm Sci 92 381. 

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

Kushner, J. IV, D. Blankschtein, and R. Langer. 2004. Experimental demonstration of the existence of highly permeable localized transport regions in low-frequency sonophoresis. J Pharm Sci 93 2733. 

Tezel A, Sens A, Tuchscherer J, Mitragotri S. Frequency dependence of sonophoresis. Pharmaceutical Research 2001, 18, 1694-1700. 

Iontophoresis and Sonophoresis In the early 1900s it was discovered that some chemical compounds could be delivered into the systemic circulation across the skin using an electric current. This phenomenon was later described as iontophoresis. Iontophoresis occurs when an electric potential difference is created across the skin layers by an electric current and this gradient drives the penetration of both charged and uncharged drugs across the skin [35],... 

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. 

Sonophoresis is another special type of US-assisted filtration in which the skin acts as a filter. 

This chapter initially deals with those solid-liquid systems in which the solid phase exists before US is applied, namely slurry formation, agglomeration and filtration, which are followed by sonophoresis, a special type of liquid-solid filtration. Then, a system where formation of the second phase is favoured by US (crystallization) is discussed, and so are systems involving a gas phase into which a liquid phase is included (nebulization), or from which it is removed (defoaming and degassing) with the aid of US complete the chapter. 

Low-frequency US, such as that used in sonophoresis, has various effects (thermai, cavitationai, acoustic streaming, dermai) on bioiogicai tissues. 

In vitro and in vivo studies on sonophoresis have allowed the variables to be optimized in developing sonophoretic experiments to be identified. Such variables pertain mainly to the irradiation source (namely, US frequency and intensity, application time and pulse length, and also the distance of the horn to the skin) others such as the nature of the permeant should also be considered, however. 

There is a proportionai — aibeit not pureiy iinear — reiationship between the amount of energy deiivered by a US device and the increase in temperature of the vehicle in contact with the skin. At a 20 khlz US frequency, US intensities above 8 W/cm significantly increases the temperature of the vehicie, viz. about 10-20°C for intensities from 8.1 to 15 W/cm at the end of a 2-h treatment — interestingly, half of the temperature rise occurs within oniy 10 min of US appiication. Tests under isothermal control have revealed that about 25% of the skin permeabiiity enhancement produced by sonophoresis can be ascribed soieiy to a thermai effect [120]. 

Unlike iontophoresis, which acts on the transporting molecules and ions, US has been shown to act on the skin barrier itself The effects of sonophoresis depend on the "quality" of the barrier that is subject to US treatment thus, barriers which are intrinsically more permeable will be more liable to physical perturbation by US and vice versa. This may explain why the most successful attempts at the US-assisted extraction of glucose across the skin involved the use of a surfactant or chemical enhancer to better "normalize" the increased transport effects observed. One of the challenges in pretreatment-type sonophoresis is that the degree of skin permeability must be determined prior to drug placement. 

When new US devices for sonophoresis are designed and constructed, their effects are checked on artificial membranes. The use of silicone membranes and over-saturated... 

---