Skin hydration - How water and osmolytes influence biophysical properties of stratum corneum
Abstract: The outermost layer of skin (i.e., the stratum corneum, SC) is the interface that separates the water-rich inside of the body from the relatively dry external environment. SC forms an effective permeability barrier, which has to be overcome in transdermal drug delivery. Its function as a barrier for molecular diffusion depends on the SC molecular structure and phase behavior. Both structure and phase behavior may be altered, for example, by hydration or addition of other solutes, which affects the barrier properties. This thesis explores the interplay between molecular properties of SC components and the macroscopic properties of the SC membrane. We investigate the influence of hydration on SC permeability at steady state by using an in vitro set-up where the boundary conditions are controlled by the water activity in the solutions in contact with the skin membrane. Changes of macroscopic properties are rationalized by employing techniques that provide information on SC molecular organization and molecular dynamics. We show that SC hydration leads to increased SC permeability, which is attributed to a higher fraction of fluid SC molecular components with lower diffusional resistance. This can have implications, for example, in transdermal delivery applications where it is desirable to increase the amount of drug delivered across the skin barrier to reach therapeutic effect. We show that common so-called moisturizers, like glycerol and urea, can be used to retain high SC permeability under dehydrating conditions. This effect is ascribed to the capability of these small polar molecules to maintain the SC molecular properties in a state that is similar to a more hydrated SC membrane at reduced hydration conditions. This result provides a deeper understanding of the beneficial effect of moisturizers in treatment of dry skin conditions and challenges the view that moisturizers, like glycerol and urea, are beneficial for skin health by merely increasing the SC hydration.
CLICK HERE TO DOWNLOAD THE WHOLE DISSERTATION. (in PDF format)