Abstract
Stratum corneum (SC), the outermost layer of skin, is the main rate limiting step in percutaneous absorption and the inter-corneocyte lipid matrix is the dominant pathway for skin permeation of solutes. Unravelling the mechanisms underpinning SC lipids barrier property is pivotal for many applications, e.g., to design better transdermal drugs, to aid skin protection from environmental chemicals, and to deliver better skin health.
Molecular dynamics (MD) simulations have been employed to predict the SC lipid matrix structural and barrier properties. However, studies that investigate how the SC lipid barrier function depends on its water content and exposure to exogenous chemicals are limited. Moreover, the partitioning of chemicals into SC lipids has been largely unaddressed. Here, MD simulations and thermodynamic modelling tools (the combined MD/COSMOmic method) are exploited to investigate the effect of hydration and exposure to chemicals on the structural and barrier property of SC lipid bilayers.
Firstly, relevant MD simulation methods to predict the free energy barrier, the diffusion coefficient, and the permeability of SC lipid bilayers are tested to assess their ability to capture SC lipids barrier property. Next, MD simulations are run to predict how the structure of SC lipid bilayers is affected by the hydration level and the exposure to topical chemicals, namely urea, glycerol, and ethanol. Results show that decreasing the hydration level lowers the ordering of the lipid leaflets. Exposure to glycerol and urea does not largely affect the structure of the bilayers. Ethanol, instead, weakens the membrane stability. Lastly, the combined MD/COSMOmic method is used to predict the partition coefficients of a set of dermatological relevant solutes. The results obtained suggest that the approach correctly reproduces the partition properties of SC lipids and that the partition enhancing features of a given molecule are related to its chemical affinity with the permeating solute.