Establishing a general atomistic model for the stratum corneum lipid matrix based on experimental data for skin permeation studies

Understanding the permeation of drugs through the intercellular lipid matrix of the stratum corneum layer of skin is crucial for effective transdermal delivery. Molecular dynamics simulations can provide molecular insights into the permeation process. In this study, we developed a new atomistic model representing the multilamellar arrangement of lipids in the stratum corneum intercellular space for permeation studies. The model was built using ceramides in extended conformation as the backbone along with free fatty acids and cholesterol. The properties of the equilibrated model were in agreement with the neutron scattering data and hydration behavior previously reported in the literature. The permeability of molecules, such as water, benzene and estradiol, and the molecular mechanism of action of permeation enhancers, such as eucalyptol and limonene, were evaluated using the model. The new model can be reliably used for studying the permeation of small molecules and for gaining mechanistic insights into the action of permeation enhancers.