Synthesis of phytoceramide analogues and evaluation of their effects on the skin barrier properties

Charles University in Prague Faculty of Pharmacy in Hradci Králové Deparment of Inorganic and Organic Chemistry Candidate: Ondřej Tesař Supervisor: doc. PharmDr. Kateřina Vávrová, Ph.D. Title of diploma thesis: Synthesis of phytoceramide analogues and evaluation of their effect on the skin barrier properties. Phytoceramides (FCER) belong to the class of sphingolipids. They are composed of a basic alcohol phytosphingosine (P) and the acyl chain. Together with the other lipids they create the extracellular membrane in human stratum corneum (SC), the uppermost layer of the skin, which protects us against the loss of water and penetration of foreign compounds into our body. The influence of FCER structure on the function of this membrane is unknown yet. Aim of the work: The aim of this work was to examine what role the acyl chain length of FCER plays in this membrane impermeability. Methods: My task was to synthetize FCER with acyl chain length of 2, 4, 6 and 24 carbons and preparation of SC model membranes containing FCER with acyl chain length of 2, 4, 6, 8 or 24 carbons, cholesterol, lignoceric acid and cholesterol sulfate. The permeabilities of the model membranes were evaluated in Franz diffusion cells. Electric impedance and permeability for two model drugs: theophylline (TH) and indomethacin..