Oleic acid concentration and effect in human stratum corneum: non-invasive determination by attenuated total reflectance infrared spectroscopy in vivo

Attenuated total reflectance infrared (ATR-IR) spectroscopy was used to study, in vivo, the mechanism of action of a putative skin penetration enhancer, oleic acid. Specifically, the spectroscopic technique monitored structural changes and enhancer concentration in the stratum corneum (SC) (skin's outermost and least permeable layer) following treatment with oleic acid in ethanol. As previously observed in vitro, oleic acid increased the hydrocarbon chain disorder of the inter-cellular lipid domains of the SC in vivo. The effects of the enhancer were prolonged but reversible. It also appeared that the treatment of the skin with oleic acid for 0.5 hour caused a gradient of effect (i.e. increased lipid disorder) that decreased from superficial to inner stratum corneum layers. However, this gradient was normalized by increasing the time of exposure of the skin to the enhancer. Although the oleic acid-induced lipid hydrocarbon chain disorder in vivo maximized at a concentration of 1% oleic acid in ethanol, the in vitro uptake of radiolabelied enhancer into excised SC increased linearly with concentration up to 10%. Further experiments showed that the saturation of response in vivo was not solubility limited. Precise analysis of the IR spectra enabled an absorption band to be assigned mainly to oleic acid and to be used, therefore, to quantity SC uptake of enhancer in vivo. A quite linear correlation between (radiochemical) in vitro and (spectroscopic) in vivo assessments of oleic acid in SC was found. Overall, then, the results reported support the conclusions: (a) that ATR-IR can monitor the effects of penetration enhancers on skin barrier function in vivo, and (b) that, in the case of oleic acid, the technique can estimate the level of enhancer within the SC as a function of time and, possibly, position.