Skin‐Protective Performance of Alternative Stratum Corneum Formed by a Pseudo‐Ceramide‐Containing Steroid Lamellar Cream

Ceramides in the stratum corneum (SC) are important for epidermal barrier function. We previously developed a synthetic pseudo-ceramide for medical (SPCM)-containing steroid cream [SPCM (+)]. This cream forms films on the skin surface and exerts anti-inflammatory effects through steroids. However, the preventive effects of this cream on the disruption of the skin barrier remained unclear. Therefore, in this study, we aimed to evaluate the protective role of SPCM (+) cream against atopic dermatitis (AD)-associated protease allergens on the skin in recovery from barrier-broken skin. We used three-dimensional (3D) skin and mouse models of disrupted skin barriers to evaluate the protective effect of SPCM (+) cream against V8 protease produced by Staphylococcus aureus. In NC/Nga mice with itching caused by living mites, SPCM (+) cream was repeatedly applied once a day for 2 weeks, and scratching behaviour was assessed every week using the MicroAct system. In the 3D skin model, the SPCM (+) cream directly blocked SC degradation by V8 protease of S. aureus and suppressed the expression of interleukin-36 gamma. The application of SPCM (+) cream to mite-parasitised mice suppressed scratching, reduced elevated activity of skin proteases, and inhibited upregulation of thymic stromal lymphopoietin. These beneficial effects of SPCM (+) cream were not observed with steroid creams without SPCM. These results suggest that the SPCM (+) cream is effective in relieving inflammation and itching by protecting the skin from proteases and allergens through its lamellar structure. This cream may be a promising treatment option for skin barrier disorders including AD and xerosis.