Diffusivity and structural polymorphism in some model stratum corneum lipid systems

Abstract

Mixtures of model stratum corneum lipids were prepared in water from cholesterol, six fatty acids and ceramides. The influence of composition on the polymorphism of these mixtures and also on the diffusivity of a model drug within them, D lip , was determined. The former was obtained from X-ray diffraction and Fourier transform infrared spectrometry, and the latter from a diffusional release model. An Lβ structure was formed for the composition approximating that of the extracellular lipids in intact human abdominal stratum corneum. D lip was independent of water content in the range 20–40% w/w, with the bilayers showing one dimensional swelling without lateral expansion. Although removal of the ceramides did not result in a significant alteration in D lip , crystalline cholesterol now appeared. The ceramides were, therefore, necessary for solubilization within the fatty acid bilayers of the large proportion of cholesterol present in the lipid fraction of intact SC. They were also responsible for a thermal L α-H II transition observed at approx. 68°. At the concentration in which it exists in intact SC, cholesterol also had only a minimal effect on D lip , but was necessary to suppress H II phase formation within the fatty acids and ensure an Lβ structure. All lipid mixtures that had an L β structure presented a diffusional barrier approx. 1 order of magnitude greater than that of an unstructured, isotropic lipid mixture. H II structures formed at cholesterol/fatty acid proportions less than approx 8:92 mol% and appeared more permeable than L β ones. All the results indicate that the diffusional barrier within the model lipid mixtures is guaranteed essentially by the presence of an L β phase. Although the ceramides and cholesterol exert no intrinsic influence on the magnitude of D lip , their presence in necessary for the existence of an L β phase at 33° that is free of both crystalline cholesterol and H II character.