Construction of pH and Temperature Dual-Responsive Ceramide Delivery System in the Stratum Corneum

Abstract

Ceramides are major components within the intercellular lamella of the stratum corneum and play an important role in the barrier function of skin. Thus, cosmetic products containing ceramides are expected to maintain and improve the skin barrier. However, maintaining the stability of ceramides within cosmetic products remains a challenge owing to their high crystallinity. Our previous study demonstrated a promising method for the incorporation of ceramides into a lotion via complexation with nonionic surfactant vesicles (i.e., niosomes). However, the stable complexation of ceramides within niosomes may interfere with their beneficial properties, because ceramides improve the skin barrier via lamella formation. Consequently, the skin moisturizing effect of the ceramide-complexed niosomes (CCNs) was insufficient. Thus, it was hypothesized that the properties of ceramide could be maximized by encouraging the collapse of the CCNs upon contact with the stratum corneum. The destabilization of nanoparticles is often achieved using stimuli-responsive polymers, which change their hydrophobicity depending on the external environment and disrupt the nanoparticle structure through hydrophobic interaction. A range of pH and temperature dual-responsive polymers (poly(MD-MAA-LT)s) was been developed in our previous study, and is responsive to the slightly acidic pH and moderately high temperature of human skin. In this study, we construct pH and temperature dual-responsive CCNs (Res-CCNs) through the modification of the CCNs with poly (MD-MAA-LT) s. The Res-CCNs were stable throughout a wide temperature range of 5 to 50°C when held at a constant pH of 6.5. However, the size of Res-CCNs increased significantly when the temperature was increased under the slightly more acidic conditions of human skin (pH of 5.0), which led to the release of ceramide. In addition, Res-CCNs showed a moisturizing effect for an extended period, when applied on human skin. This novel approach to the application of ceramides is expected to promote the benefits of ceramides in the skin care field.