Acoustic streaming simulation and analyses in in vitro low frequency sonophoresis

•Demonstrating the velocity of acoustic streaming is another important physical effect for the improvement of in vitro LFS.•When transducer horn was away from the skin surface, the velocity of acoustic streaming increased first and then decreased.•The spatial synthesis effect of acoustic streaming may be another key factor for permeation's enhancement.

Low frequency sonophoresis (LFS) is a type of transdermal drug delivery method, which is useful for enhancing the permeation of hydrophobic and hydrophilic compounds across the skin. At present, the main ultrasonic effects of LFS include cavitation, microstreaming from bubbles, thermal effects, and recently bilayer sonophore effect, in which cavitation effect has been studied to interpret LFS principle since 2003. However, our experimental results show that the acoustic streaming is another factor in high-intensity acoustic input. Therefore, a calculation model is built up based on acoustic equation and turbulence k-ε model in terms of the finite element software COMSOL Multiphysics. In vitro LFS experiment consists of a Langevin-type ultrasonic transducer working at 21 kHz and a Franz diffusion system, and Calcein permeations were measured at different acoustic intensities and distance between the transducer horn and skin. Calculated and experimental results demonstrate that the velocity of acoustic streaming in the donor is another important physical effect for the improvement of LFS. When the increase of acoustic intensity can enlarge the acoustic pressure and velocities of acoustic streaming, and enhance Calcein permeation at the same time; However, when the transducer horn was away from the skin surface, the acoustic pressure decreased but the velocity of acoustic streaming increased first and then decreased, and the latter varying tendency is in accordance with Calcein permeation change. Furthermore, calculated results of the line integral along the radial velocity show that spatial synthesis effect of acoustic streaming velocity may be the key factor for the enhancement of Calcein permeation other than the maximum velocity value. Therefore, it can be recognized that the acoustic streaming resulting from the transducer horn may be another important influence factor in in vitro LFS, especially in high acoustic intensity input (>1 W/cm2).