LOW-INTENSITY ULTRASOUND AS A PROBE TO ELUCIDATE THE RELATIVE FOLLICULAR CONTRIBUTION TO TOTAL TRANSDERMAL ABSORPTION

Purpose. To investigate the effect of ultrasound on the histological i ntegrity and permeability properties of whole rat skin in vitro. Metho ds. A defined, field-free source of ultrasound was used to irradiate e xcised rat skin prior to in vitro transport studies in Franz-type cell s using sucrose, mannitol, hydrocortisone, 5-fluorouracil and aminopyr ine. Results. High intensity ultrasound irradiation (1 to 2 W cm(-2)) irreversibly damaged cutaneous structures and increased the percutaneo us transport rate of permeants. In contrast, skin integrity was largel y maintained with low intensity ultrasound (0.1 to 1 W cm(-2)) which m erely discharged sebum from the sebaceous glands so as to fill much of the hair follicle shafts. This effect caused the transfollicular abso rption pathway to be blocked for hydrophilic molecules that penetrate via this route and reduced the transport rate significantly. Conclusio ns. This phenomenon may be used as a probe to elucidate the relative f ollicular contribution to total penetration for hydrophilic permeants. It was demonstrated that the shunt pathway was responsible for virtua lly all mannitol and sucrose penetration, perhaps half of hydrocortiso ne transport but negligible aminopyrine and 5-fluorouracil penetration .