Thermal analyses of in vitro low frequency sonophoresis

As a type of transdermal drug delivery method, low frequency sonophoresis (LFS) has been investigated during the last twenty years and is currently being attempted in a clinical setting. However, the safety of low frequency ultrasound on humans has not been completely guaranteed with high-intensity ultrasound. Thermal damage, one of the challenges in the LFS process, e.g., burns, epidermal detachment and necrosis of tissues, hinders its widespread applications. To predict and impede the overheating problems in LFS, an acoustic-flow-thermal finite element method (FEM) based on COMSOL Multiphysics software is proposed in this paper to achieve thermal analyses. The temperature distribution and its rising curves in in vitro LFS are obtained by the FEM method and experimental measurements. Both simulated and experimental maximum temperatures are larger than the safety value (e.g., 42°C on human tissues) when the driving voltage is higher than 40V (5.5W input electric power), which proves that the overheating problem really exists in high-intensity ultrasound. Furthermore, the results show that the calculated temperature rising curves in in vitro LFS correspond to the experimental results, proving the effectiveness of this FEM method. In addition, several potential thermal influence factors have been studied, including a duty ratio and amplitude of the driving voltage, and liquid height in the donor, which may be helpful in restraining the temperature increase to limit thermal damage. According to the calculated and experimental results, the former two factors are sensitive to the rise in temperature, but a small scale of liquid volume increase can enhance the permeation of Calcein without obvious temperature change. Hence, the above factors can be synthetically utilized to restrain the rise in temperature with little sacrifice of permeation ability. So this acoustic-flow-thermal FEM method could be applied to an optimized LFS system design and simulating the thermal analyses of LFS in healthy human body in terms of safe thermal limits.