The Mechanism of Sonophoresis and the Penetration Pathways

Sonophoresis uses ultrasound as a physical enhancer for systemic transdermal drug delivery (TDD). Low-frequency sonophoresis in the range of 20–100 kHz has been demonstrated to enhance the transdermal delivery of various low-molecular weight drugs and high-molecular weight proteins across the human skin. The bioeffects of ultrasound in tissues are mediated by thermal and nonthermal effects. Ultrasound-induced skin heating causes fluidization of stratum corneum (SC) lipids, facilitating transdermal permeation of molecules. Cavitation is the nonthermal effect of ultrasound and is believed to be the main mechanism of enhanced transdermal delivery in sonophoresis, by creating shock waves and acoustic micro-jets on the SC surface. Among the three different percutaneous penetration pathways including the intercellular, transcellular, and follicular penetration routes, both intercellular and transcellular pathways are primarily created and facilitated during ultrasound exposure for TDD. Sonophoresis may act synergistically with various other physical and chemical penetration enhancement methods in promoting transdermal drug delivery. The ratio of frequency and peak rare-fractional pressure, the distance between the surface of transducer and the skin surface, and the properties of the coupling medium such as the viscosity, density, acoustic impedance and the composition of the gas and liquid phases are factors affecting the efficacy of TDD using ultrasound. Sonophoresis has been widely used for TDD, such as transcutaneous immunization and gene therapy and as a noninvasive transdermal monitoring method. In addition, sonophoresis represents a safe and effective method for TDD.