Polar emollients in cosmetic formulations enhance the penetration and biological effects of Phytosphingosine on skin

Recent cosmetic and dermatological science focuses on active ingredients in order to support the biological function of the skin such as protection against physical and chemical stress, UV-irradiation and microbes. Keratinocytes represent key elements of this barrier since they form the outer water-impermeable layers of the skin. To assure this function keratinocytes run through a special differentiation process from stratum basale to the stratum corneum, which is formed only of end-differentiated keratinocytes, now called corneocytes. The other main constituent of the water-impermeable barrier of the skin are barrier lipids i.e. ceramides, cholesterol and free fatty acids. Ceramides are formed by keratinocytes by amidation of sphingoid bases such as Phytosphingosine with fatty acids. Furthermore, Phytosphingosine is a natural antimicrobial compound and it is involved in several cellular processes such as cell differentiation and anti-inflammation. Based on this information the present study was aimed to evaluate the effects of Phytosphingosine as an active ingredient in cosmetic formulations. Furthermore, here we investigated whether the type of formulation influences the biological activity of Phytosphingosine. For this purpose cultured keratinocytes were incubated with Phytosphingosine and gene expression profiling was performed using DNA micro arrays. Gene expression profiling revealed that Phytosphingosine significantly promotes cell differentiation. Additionally penetration studies with Phytosphingosine formulated with cosmetic oils of different polarity were carried out using dermatomed pig skin in Franz cells. Penetration experiments clearly showed that the biological skin delivery of this active ingredient markedly depends on the polarity of the utilized emollient with best penetration abilities for polar oils. Further evaluation of the biological effects of Phytosphingosine was accomplished by applying the different formulations on in vitro reconstructed human epidermis with subsequent RT-qPCR analysis of selected genes that are typical for keratinocyte differentiation. Using this approach we were further able to demonstrate that the biological effect of Phytosphingosine on keratinocyte differentiation in reconstructed human epidermis is clearly dependent on the bioavailability, which in turn is determined by the polarity of the cosmetic oil. In conclusion, we here demonstrate that Phytosphingosine promotes keratinocyte differentiation and, therefore, is an ideal active ingredient for cosmetic applications whose biological activity can be enhanced by the use of an appropriate formulation. (C) 2008 Elsevier B.V. All rights reserved.