Ultrasound transdermal drug transport

Tang H, Wang CCJ, Blankschtein D, and Danger R. An investigation of the role of cavitation in low-frequency ultrasound-mediated transdermal drug transport. Pharm. Res. 2002 19 1160-1169. 

Langer, R. Determination of threshold energy dose for ultrasound-induced transdermal drug transport. J. Controlled Release 2000, 63, 41-52. 116. 

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. 

Application of ultrasound enhances transdermal drug transport, a phenomenon referred to as sonophoresis. Proper choice of ultrasound parameters including ultrasound energy dose, frequency, intensity, pulse length, and distance of transducer from the skin is... 

This hypothesis also explains why low-frequency ultrasound can induce transdermal transport of drugs which exhibit very low passive transport. Drugs possessing low passive permeabilities are either i) hydrophilic, which makes their partitioning into the SC bilayers difficult or ii) large in molecular size (for example, proteins), which reduces their diffusion coefficients in the SC. Low-frequency ultrasound may overcome both of these limitations by providing aqueous transport channels across the skin. Since these channels are filled with saline, hydrophilic drugs can easily partition into the SC. In addition, diffusion of... 

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