Foreign molecules in biomembranes : Molecular effects on intact stratum corneum and model lipid systems

Abstract: The skin is our largest organ and its main function is to protect us from uptake of foreign chemicals and from desiccation. The barrier function of the skin is mainly assured by its outermost layer, the stratum corneum (SC). When one wants to deliver a compound into or through the skin, for example in (trans)dermal drug delivery and cosmetics, one generally needs to make the skin more permeable. Therefore, it is desirable to control the skin barrier function. The purpose of this thesis is to deepen the understanding of the mechanisms that determine the skin permeability at a molecular level. The focus is laid on the molecular mobility and fluidity of components in SC, which play crucial roles in the barrier property. One major goal was to characterize the fluid SC fractions and how they vary with different conditions, for example, hydration, temperature, addition of moisturisers and penetration enhancers, solvents and in diseased skin, for example, psoriasis. The molecular information can be related to other macroscopic properties of the skin, for example, water-holding capacity, elasticity, softness, dryness, and barrier function. The findings of this research can be applied in topical formulations for drug delivery and skin care products as well as for treatment of diseased skin. These results were achieved by performing experiments on intact SC, extracted corneocyte and model lipid systems and by combining different complementary techniques like NMR (nuclear magnetic resonance), scattering, calorimetry, sorption microbalance and diffusion-cell systems.