Cholesterol sulfate and calcium affect stratum corneum lipid organization over a wide temperature range

The main diffusion barrier for drugs penetrating through the skin is locate d in the intercellular lipid matrix in the upper layer of the skin, the str atum corneum (SC), The main lipid classes in the SC are ceramides (CER), fr ee fatty acids (FFA) and cholesterol (CHOL). The lipids in SC are organized into two lamellar phases with periodicities of approximately 13 and 6 mn, respectively. Similar Lipid organization has been found with equimolar CHOL :CER:FFA. mixtures in SAXD studies performed at room temperature. However, one may conclude that the phase behavior of the mixtures is similar to that in SC only when the lipid organization of the lipid mixtures resembles tha t in SC over a wide temperature range. Therefore, in the present study, the organization of the lipid mixtures has been studied in a temperature range between 20 degrees and 95 degrees C. From these ex experiments it appeared that at elevated temperatures in equimolar CHOL:CER:FFA mixtures a new pro minent 4.3 nm phase is formed between 35-55 degrees C, which is absent or o nly weakly formed in intact human and pig SC, respectively. As it has been suggested that gradients of pH and cholesterol sulfate exist in the SC and that Ca2+ is present only in the lowest SC layers, the effect of pH, choles terol sulfate, and Ca2+ on the lipid phase behavior has been investigated w ith lipid mixtures. Both an increase in pH from 5 (pH at the skin surface) to 7.4 (pH at the SC-stratum granulosum interface) and the presence of chol esterol sulfate promote the formation of the 13 nm lamellar phase. Furtherm ore, cholesterol sulfate reduces the amount of CHOL that is present in crys talline domains, causes a shift in the formation of the 4.3 mm phase to hig her temperatures, and makes this phase less prominent at higher temperature s. The finding that Ca2+ counteracts' the effects of cholesterol sulfate in dicates the importance of a proper balance of minor SC components for appro priate SC lipid organization. In addition, when the findings are extrapolat ed to the in vivo situation, it seems that cholesterol sulfate is required to dissolve cholesterol in the lamellar phases and to stabilize SC lipid or ganization. Therefore, a drop in cholesterol sulfate content in the superfi cial layers of the SC is expected to destabilize the lipid lamellar phases, which might facilitate the desquamation process.-Bouwstra, J. A., G. S. Go oris, F. E. R. Dubbelaar, and M. Ponec. Cholesterol. sulfate and calcium af fect stratum corneum lipid organization over a wide temperature range.