Ceramides and Dimethylamino Acid Derivatives as Skin Barrier Modulators

The purpose of this work is to contribute to the understanding of the structure-activity relationships and behavior of the skin ceramides and transdermal penetration enhancers based on dimethylamino acid esters. First two chapters provide a theoretical background for understanding the main principles of transdermal drug delivery as well as composition and function of stratum corneum barrier. The experimental work is presented in the form of individual publications in chapters three to five. The first chapter describes transport routes through the human skin and gives an overview of enhancers of transdermal permeation with main accent on their chemical structure, mechanism of action, interaction with stratum corneum components and advantages and drawbacks of their use. The second chapter brings more detailed information on the specific content and composition of stratum corneum. The main attention is paid to the ceramides - a complex group of lipids that play a crucial role as cell signaling molecules and skin barrier constituents. In the skin, these sphingolipids form a major part of the stratum corneum intercellular lipid matrix, which is the barrier for penetration of most compounds. The development of such a protective layer was a critical step in the evolution of life on a dry land. Moreover,..