ABSTRACT
PURPOSE: The objective of this study was to evaluate the utility of a stratum corneum substitute (SCS) as a novel in vitro percutaneous penetration model. The SCS consists of synthetic stratum corneum (SC) lipids (cholesterol, free fatty acids, and specific ceramides) applied onto a porous substrate. The composition, organization, and orientation of lipids in the SCS bear high resemblance to that of the intercellular barrier lipids in SC. METHODS: The barrier integrity of the SCS was evaluated by means of passive diffusion studies, using three model compounds with different lipophilicities. The effects of lipid layer thickness, permeant lipophilicity, and altered lipid composition on the barrier properties were investigated, using isolated human SC as a control sample. RESULTS: For all three model compounds, the permeability characteristics of the SCS with a 12-mum-thick lipid layer closely resemble those of human SC. Modification of the lipid composition, generating an SCS that lacks the characteristic long periodicity phase as present in SC, was accompanied by a 2-fold increased permeability. CONCLUSIONS: The SCS offers an attractive tool to predict solute permeation through human skin. Moreover, as its lipid composition can be modified, they may also serve as a suitable screening model for diseased skin.
Subject(s)
Benzocaine/metabolism , Epidermis/metabolism , Lipid Bilayers/metabolism , Skin Absorption , Sunscreening Agents/metabolism , para-Aminobenzoates , 4-Aminobenzoic Acid/administration & dosage , 4-Aminobenzoic Acid/chemistry , 4-Aminobenzoic Acid/metabolism , Administration, Cutaneous , Benzocaine/administration & dosage , Benzocaine/chemistry , Ceramides/chemistry , Cholesterol/chemistry , Diffusion , Diffusion Chambers, Culture , Epidermis/ultrastructure , Fatty Acids, Nonesterified/chemistry , Humans , Lipid Bilayers/chemistry , Permeability , Sunscreening Agents/administration & dosage , Sunscreening Agents/chemistry , Time FactorsABSTRACT
The intercellular stratum corneum (SC) lipids form the main barrier for diffusion of substances through the skin. A porous substrate covered with synthetic SC lipids would be an attractive model to study percutaneous penetration, hereby replacing native human SC. Prerequisite is that this stratum corneum substitute (SCS) is prepared with a uniform lipid composition and layer thickness. Furthermore, the lipid organization and orientation should resemble that in SC. The objective of this study was to investigate the utility of an airbrush spraying device to prepare a SCS composed of cholesterol, ceramides and free fatty acids on a polycarbonate filter. The results demonstrate that a proper choice of solvent mixture and lipid concentration is crucial to achieve a uniform distribution of the applied lipids over the filter surface. A smooth and tightly packed lipid layer is only obtained when the equilibration conditions are appropriately chosen. The SCS possesses two crystalline lamellar phases with periodicities similar to those present in native SC. The orientation of these lamellae is mainly parallel to the surface of the polycarbonate filter, which resembles the orientation of the intercellular SC lipids. In conclusion, the airbrush technique enables generation of a homogeneous SCS, which ultimately may function as a predictive in vitro percutaneous penetration model.
