Sonophoresis studies

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. 

Sonophoresis (or phonophoresis) is a technique to enhance percutaneous penetration via the application of ultrasonic energy. Review of the sonophoresis literature, however, shows that the effects of ultrasound have been variable. For example, largely unsuccessful earlier studies with various common drugs used ultrasound frequencies of 1-3 MHz at 1-3 W/cm [67,68], whereas a... 

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. ... 

Sonophoresis has employed three distinct categories of US high-frequency or diagnostic US (2-10 MHz), mid-frequency or therapeutic US (0.7-3 MHz), and low-frequency US (5-100 kHz). It appears, from a general overview of the literature, that the efficiency of US-mediated drug delivery depends on several factors, including US frequency, intensity (i.e., power per unit area), continuous versus pulsed mode, duty cycle, duration, coupling medium, and so on. The fact that very few studies have used common values for some or any of these parameters almost certainly accounts for the different and sometimes contradictory results in the public domain. 

Ultrasound at various frequencies in the range of 20 kHz to 16 MHz has been used for sonophoresis. These studies of sonophoresis can be classified into three categories based on the ultrasound frequency used, i.e., therapeutic, high-frequency, and low-frequency ultrasound. 

In a recent systematic study of the dependence of 20 kHz sonophoresis on ultrasound parameters, Mitragotri et al. showed that the enhancement of skin permeability varies linearly with ultrasound intensity and ultrasound on-time (for pulsed ultrasound, ultrasound on-time equals the product of total ultrasound application time and duty cycle), while is independent of the ultrasound duty cycle. Based on those findings, fhe authors reported that there is a threshold energy dose for ultrasound induced transdermal drug transport. Once the threshold value is crossed, the enhancement of skin permeability varies linearly with the ultrasound energy dose (J/cm ), which is calculated as the product of ultrasound intensity and ultrasound on-time. This result indicates that ultrasound energy dose can be used as a predictor of the effect of 20 kHz sonophoresis. The authors also indicated that it is important to determine the threshold energy dose for each individual sonophoresis system, for example, the real in vivo situation, because it may vary from system to system. Specifically, it may vary between different skin models, as well as with the ultrasound frequency and the distance of the transducer from the skin surface, etc. 

The most commonly used technique of sonophoresis in these studies was to apply hydrocortisone in the form of an ointment on the skin and then apply ultrasound by keeping the transducer in contact with the ointment. In some cases, the transducer was moved in circular patterns to avoid a continuous exposure of a certain part of the skin to ultrasound. Although these studies were performed using different animal models, application techniques, hydrocortisone concentrations in the ointment, and exposure time, a measurable enhancement of hydrocortisone transport was reported in almost all cases. In contrast, most of the attempts to enhance transdermal transport of lidocaine and salicylates have been less successful. In the case of lidocaine, the sonophoretic enhancement was measured in terms of reduction of onset time for anesthesia or prolonging duration of anesthesia. In most cases, no significant effect of ultrasound application on either induction time or duration of anesthesia has been reported. Similarly sonophoresis of salicylates from ointments has not been found to induce any significant increase in plasma salicylate levels. ... 

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