Use of a model lipid matrix to demonstrate the dependence of the stratum corneum's barrier properties on its internal geometry

Abstract

An attempt was made to confirm the relative importance of the stratum corneum's internal geometry and extracellular lipid permeability for its barrier properties. Drug diffusivity, D lip , was first measured in a structured matrix composed of model stratum corneum lipids by using a simple release model. Although the values obtained depended on the lipid composition, they all lie within the range 10 −9–10 −8 cm 2/s and must be considered as spatially-averaged values over all existing bilayer orientations. The effective drug diffusivity, D eff , within excised human stratum corneum was then determined from permeation data using the applicable solution to the diffusion equation for an isotropic membrane. From these two results it was possible to calculate an experimental ratio of D lip to D eff of 6.6 × 10 3. This value is considered to be greater than unity by reason of the internal geometry of the stratum corneum, where an extended diffusional pathlcngth and reduced diffusional area exist when compared with an isotropic membrane. A model was then developed to simulate the influence of the internal geometry of the stratum corneum on D/ D eff , where D is now diffusivity within the extracellular lipid pathway. The model is tailored specifically to allow variation of those dimensions thought to be of importance for drug permeation, i.e. stratum corneum thickness and lipid content, as well as corneocyte diameter and thickness. The theoretical values for D/ D eff obtained with this model lie in the range 10 2–10 4 and, hence, can account for the experimentally determined value of D lip/ D eff. The simple model and methods adopted in this study thus provide a useful insight into the stratum corneum's barrier properties. Clearly, many questions are left unanswered, for example, the importance of anisotropic diffusional relaxation within the extracellular lamellar lipid structure.