Influence of ceramides in the solubilization of stratum corneum lipid liposomes by C₁₂-betaine/sodium dodecyl sulfate mixtures

Abstract

The solubilization of liposomes modeling the stratum corneum (SC) lipid composition and those obtained varying the proportion of ceramides by means of dodecyl betaine (C₁₂-Bet)/sodium dodecyl sulfate (SDS) mixtures was studied. The surfactant/lipid molar ratios (Re) and the bilayer/aqueous phase partition coefficients (K) were determined by monitoring the changes in the static light scattering of the system during solubilization. The fact that the free surfactant concentration was always similar to its critical micelle concentration (CMC) indicates that the liposome solubilization was mainly ruled by the formation of mixed micelles. The mole fraction of the zwitterionic component (X_zwitter) of 0.4 showed the lowest ability to saturate or solubilize liposomes, although exhibiting the highest degree of partitioning into liposomes. This X_zwitter corresponded to the highest derivation of the CMCs of these mixtures (negative synergism) and to the highest reduction in the skin irritation with respect to the anionic component. Higher and lower proportion of ceramides in the mixture led to a fall and to a rise in both the activity and the partitioning of a specific surfactant mixture (X_zwitter=0.4). This finding could be related to the recently reported dependences of the level of ceramides in skin and function barrier abnormalities. Comparison of the present Re and K values with those reported for phosphatidylcholine (PC) liposomes shows that, although SC liposomes were more resistant to the action of surfactant mixtures, the surfactant partitioning into SC bilayers was similar to that reported for PC ones in all cases.

Introduction

One of the key functions of stratum corneum (SC) lipids is to maintain the permeability barrier of the skin (Elias, 1981, Grubauer et al., 1989). It has been established that the perturbations in the organized structure of these lipids affect the skin barrier function (Harada et al., 1992, Lavrijsen et al., 1995). Changes in the lipid composition are associated with different skin symptoms. Thus, there is a marked decrease in ceramide level in patients with atopic dermatitis, suggesting that an insufficiency of this lipid is an etiological factor in atopic dry and barrier-disrupted skin (Holleran et al., 1991, Murata et al., 1996, Ponec et al., 1997). However, a physico-chemical confirmation of this barrier abnormality using a simplified membrane model such as liposomes is still lacking.

The interaction of surfactants with liposomes has been extensively studied (Polozava et al., 1995, Inoue, 1996, Partearroyo et al., 1996, Silvander et al., 1996). This process leads to the breakdown of lamellar structures and to the formation of lipid–surfactant mixed micelles. A significant contribution has been made by Lichtenberg et al. (1985), who postulated that the effective surfactant/lipid molar ratio (Re) producing solubilization of liposomes depends on the surfactant critical micelle concentration (CMC) and on the bilayer/aqueous medium distribution coefficients.

In previous studies, Wertz and co-workers (Wertz et al., 1986, Wertz, 1992) and Downing et al. (1993) prepared liposomes from lipid mixtures approximating the SC composition and studied their interaction with sodium dodecyl sulfate (SDS) to determine the deleterious effect of this surfactant on human skin.

Zwitterionic surfactants have strong interaction with anionic surfactants in water (Iwasaki et al., 1991). The effect of the micellar solution phase of these mixtures in avoiding or at least reducing the level of anionic/protein interaction has been suggested by several workers as a way of slowing down the irritation potential of the anionic surfactants (Garcı́a Domı́nguez et al., 1981, Cooper and Berner, 1985). Thus, a reduction in the skin irritation by anionics has been reported in the presence of amphoteric surfactants (Rhein and Simion, 1991).

We studied the formation of liposomes using a mixture of four lipids modeling the composition of SC and the sublytic interactions of dodecyl betaine (C₁₂-Bet), SDS, and mixtures of these surfactants with SC liposomes (de la Maza et al., 1995, de la Maza and Parra, 1996, de la Maza et al., 1997, de la Maza et al., 1998). In the present work we seek to extend these investigations by characterizing the Re and K parameters of C₁₂-Bet/SDS mixtures when saturated and solubilized SC liposomes, as well as the influence of proportion of ceramides on these parameters. This information may be useful to evaluate the activity changes of these surfactant mixtures with respect to that of the anionic component on a simplified SC membrane model and to clarify the aforementioned correlation between the presence of ceramides in skin and the abnormalities in the barrier function.