Mimicking the human stratum corneum barrier: a biomimetic brick-and-mortar model for in vitro permeation study

Abstract The development of reliable in vitro models for stratum corneum (SC) permeation studies remains a significant challenge. Ethical constraints, interspecies disparities, and inter-individual variability in skin underscore the need for standardized skin equivalents with significant research and commercial value. Conventional artificial skin models typically lack the characteristic ‘brick-and-mortar’ structure of the SC, the primary barrier of the skin, leading to measurable functional deviations from native tissue. To address this gap, we developed a biomimetic SC (ASC) that faithfully replicates the brick-and-mortar structure of the human SC. Polymer microspheres of a size mimicking corneocytes—composed of an optimized ternary polycaprolactone/poly(methyl methacrylate)/polyhydroxybutyrate blend—served as ‘bricks’ embedded within a lipid-based ‘mortar’ via a thermally assisted compression molding process. The resulting ASC demonstrated barrier properties comparable to those of excised human epidermis membrane (HEM). Permeability coefficients for five model drugs of diverse properties showed a Pearson’s correlation of r > 0.99 between ASC and HEM. Molecular simulations further elucidated the enhanced intermolecular interactions and restricted drug diffusion within the optimized polymer matrix. Furthermore, the ASC exhibited storage stability, maintaining consistent barrier properties over four weeks at −20 °C. This structurally biomimetic ASC represents a promising, predictive, and animal-free platform for in vitro permeation testing.