Localization of lipophilic molecules penetrating rat skin in vivo by quantitative autoradiography

A microcomputer-based image analysis autoradiographic method was used to characterize drug penetration profiles and drug localization in the various regions of the rat skin. By means of this quantitative autoradiographic method, it was possible to measure and visualize the effect of carriers and application time on the localization in the rat skin of two lipophilic compounds, tetrahydrocannabinol (THC) and oleic acid (OA). It was found that after 2 h, both compounds, THC and OA, show a similar profile of penetration: relatively low concentrations accumulated in the various layers of the skin. No significant difference (p < 0.4) was found between the concentration in the epidermis and in the appendages, either for THC or OA. The epidermis and the appendages contained twice the concentration measured in the dermis. After 24 h, a different behavior can be described for each compound. It appears that from the same carrier, Transcutol, THC has a much greater skin penetration, as well as a different localization, than OA. For THC, a concentration gradient can be observed from the epidermis through the appendages to the dermis. It appears that by increasing the time of application from 2 to 24 h, the preference of a molecule to 'choose' the penetration routes can be emphasized. It was also shown that a penetration enhancing agent such as oleic acid may affect the localization of THC in the various skin layers. The highest concentration of drug was found in the epidermis and appendages.