Novel Preparation of Intercellular Lipid Models of the Stratum Corneum Containing Stereoactive Ceramide

Abstract

The stratum corneum, the outermost layer of the skin, plays the main barrier for the drug permeation via the skin. The barrier function of the stratum corneum is dominated by the microstructure formed by intercellular lipids in the stratum corneum consisting of ceramide (CER), cholesterol (CHOL), fatty acids, and their derivatives. The lipid microstructure, the molecular arrangement of intercellular lipids in the stratum corneum, has been investigated using synchrotron X-ray scattering and neutron diffraction.1-3) Two kinds of lamellar structures were observed by small angle Xray scattering (SAXS) and neutron diffraction. One of them is a short lamellar structure with a repeat distance of about 6 nm, and the other is a long one with a repeat distance thought to be about 13 nm. 4) On the other hand, hydrocarbon chain packing was obtained by wide angle X-ray scattering (WAXS). Hexagonal hydrocarbon chain packing with a lattice distance of about 0.42 nm and orthorhombic packing with lattice distances of about 0.42 nm and 0.37 nm have been observed.5) The correlation between lamellar structure and hydrocarbon chain packing was investigated by simultaneous measurements using SAXS and WAXS employing differential scanning calorimetry.6) It is assumed that these two kinds of hydrocarbon chain packing were determined by the unbalance of the lipid compositions of intercellular lipid in stratum corneum. Moreover, stratum corneum lipid components at the surface were found to be different from those at a deeper position. 7) Recently, the distribution of the lipid components and microstructures in stratum corneum was focused on the various groups to clarify the relationship between microstructure and barrier function of the skin. [8][9][10] But, the correlation between lipid composition and the resulting microstructure formation of intercellular lipids in the stratum corneum is not yet fully understood.To develop the effective transdermal drug delivery systems and cosmetics, it is important to determine the characteristics of the intrinsic lipid microstructure in stratum corneum and the alteration of lipids in the stratum corneum caused by administration of components in pharmaceutical or cosmetic formulations. Although many studies have been performed to clarify the effect of chemical permeation enhancers on the lipid microstructure of the stratum corneum, 11,12) the use of natural stratum corneum is rather difficult because of its noisy background. The microstructure of stratum corneum lipids has a diversity that enables it to act as a barrier to dehydration and to the invasion of foreign hazards. A simplified model is necessary to investigate the understanding the diversity of the microstructure and the molecular interaction between the stratum corneum lipids and chemical enhancers.Lipid mixtures of various types of CERs/CHOL/free fatty acids have been prepared as models of the intercellular lipids in the stratum corneum. [13][14][15][16] It has already been clarified that CER1 with a long chain fatty acid side chain is im...

In vivo evaluation of lateral lipid chain packing in human stratum corneum

“…where q 15.08 is the integrated intensity of the diffraction peak at q = 15.08 nm −1 and q 16.78 is that of the peak at q = 16.78 nm −1 . The parameter q 16.78 corresponds to the signal of orthorhombic hydrocarbon chain packing.…”

Effect of Nerolidol and/or Levulinic Acid on the Thermotropic Behavior of Lipid Lamellar Structures in the Stratum Corneum

“…The former is derived from hexagonal and orthorhombic structures, and the latter is derived from only orthorhombic structures. 15,23,25) Figure 1 presents the synchrotron X-ray diffraction results for hairless mouse stratum corneum treated with water (W), 3.0% (w/w) levulinic acid (L3), 1.0% (w/w) nerolidol +3.0% (w/w) levulinic acid (N1L3), and 1.0% (w/w) nerolidol (N1) at 20°C. The profile of L3 was nearly identical to that of W. By contrast, the stratum corneum treated with nerolidol (N1, N1L3) exhibited a significant decrease in intensity, and gel lipids occurred near 2.2 nm…”

Physicochemical Analysis of Liposome Membranes Consisting of Model Lipids in the Stratum Corneum

“…In light of the disappearance of lateral packing at 60 after 1 h, as shown by SAXS, it is possible that packed lipids are annealing when the model lipids are exposed to a certain higher temperature for a certain period of time. H. Watanabe et al demonstrated that the phase diagram of Cer 5 2-hydroxyacyl sphingosine /Chol/PA i.e., Cer 5/ Chol/PA bilayer was classifi ed into 4 clusters, with no distinct phase transition temperature observed in cluster 3, as measured by fluorescence anisotropy 20 . The liposomes used in our present studies, consisting of Cer 2 non-hydroxyacyl sphingosine /Chol/PA at 12.5/34.5/53, correspond to cluster 3 in their phase diagram.…”