The “weight” of skin structure and lipidomics on percutaneous absorption of xenobiotics

Molecules can successfully penetrate and permeate skin barrier in relation to their physicochemical characteristics, such as partition coefficient and molecular weight. Nevertheless, skin absorption process is also affected by the highly variable characteristics of skin and by the integrity its upper layers. This latter aspect is particularly critical for ex-vivo skin samples used in in vitro permeation studies. Aiming to better understand how the membrane variability can affect the results of in vitro permeation studies, the impact of structural characteristics of human epidermis (weight, thickness, electrical resistance properties, storage time) and lipid composition of stratum corneum on the permeation profiles of model molecules were matter of investigation. In line with OECD guideline on in vitro absorption studies, caffeine (log Pow 0.01) and benzoic acid (log Pow 1.83) were used as models, having different lipophilicity. In vitro skin permeation experiments were performed based on Franz diffusion cell and, as a membrane, human epidermis from different donors. The lipid composition of stratum corneum sheets coming from the same donors was obtained by shotgun lipidomics, an analytical approach in which total lipid extracts of tissues are directly infused into a tandem mass spectrometer (triple quadrupole). This approach allows us to detect (and in some cases semi-quantify) about hundred different molecular species, belonging to at least seven lipid classes. The stratum corneum lipid profile obtained was successfully correlated with permeability data.