The mechanism of stratum corneum (SC) permeabilization by ultrasound (
sonophoresis) is unknown. We studied here permeation pathways, and SC
intercellular structural organization following applications of high-f
requency sonophoresis to hairless mouse skin. Ruthenium tetroxide post
-fixation and tracer solutions of LaNO3 and FITC-dextrans were employe
d to examine SC lamellar bilayers, lamellar body morphology and subcel
lular permeation pathways. Sonophoresis disrupted the compact organiza
tion of SC bilayers and LB-derived contents at the stratum granulosum
(SG)-SC interface, leading to domain separation between 0 and 20 h, re
verting by 48 h. Post-sonophoresis, tracers traversed the SCvia lacuna
e within the lamellar bilayers, and via lamellae in sites that display
ed domain separation. These studies provide insights about the penetra
tion pathways, permeabilizing mechanisms, and kinetics of sonophoresis
on the epidermis.