Lipid Biomimetic Models As Simple Yet Complex Tools to Predict Skin Permeation and Drug–Membrane Biophysical Interactions

The barrier function of the skin is primarily determined by its outermost layer, the Stratum Corneum (SC). The SC consists of corneocytes embedded in a lipid matrix composed mainly of ceramides, cholesterol, and free fatty acids in equimolar proportions and is organised in a complex lamellar structure with different periodicities and lateral packings. This matrix provides a diffusion pathway across the SC for bioactive compounds that are administered to the skin. In this regard, and as the skin administration route has grown in popularity, there has been an increase in the use of lipid mixtures that closely resemble the SC lipid matrix, either for a deeper biophysical understanding or for pharmaceutical and cosmetic purposes. This review focuses on a systematic analysis of the main outcomes of using lipid mixtures as SC lipid matrix models for pharmaceutical and cosmetic purposes. Thus, a methodical evaluation of the main outcomes based on the SC structure is performed, as well as the main recent developments in finding suitable new in vitro tools for permeation testing based on lipid models.