Generation and growth of bilayer defects induced by ultrasound

Transdermal drug delivery is handicapped by the low skin permeability caused by highly ordered structure of lipid bilayers in the outer human skin layer. It has been reported that ultrasound can increase the permeability of human skin. The enhancement was attributed to acoustic cavitation but the underlying physical mechanism is not fully understood. As a model, dipalmitoylphosphatidylcholine (DPPC) lipid bilayers are insonicated by ultrasound of two submegahertz frequencies (168 kHz and 707 kHz). The free-field spatial peak pressure amplitudes of both are measured to be ${\text{6×10}}^5\hspace{0.17em}\mathrm{Pa}.$ Bilayer defects, which have average diameters of tens to hundreds of nanometers and can be detected by an atomic force microscope, are generated within less than 0.5 min. The number of the defects grows with time. The defect growth rate at the 168-kHz frequency is about 3.5 times that at the 707-kHz frequency.