ABSTRACT

The skin is composed of several morphologically distinct layers. The skin is protected primarily by the stratum corneum (SC). The superficial region, which is only 10-20 mm thick, is the primary barrier to the percutaneous absorption of compounds, as well as to water loss. Underlying the SC is the viable epidermis (50-100 mm thick), which is responsible for generation of the SC. The dermis (1-2mm thick) is directly adjacent to the epidermis and provides the mechanical support for the skin. The viable epidermis is a stratified squamous epithelium consisting of basal, spinous, and granular cell layers. Each layer is defined by position, shape, morphology, and state of differentiation of keratinocytes. The epidermis is a dynamic, constantly self-renewing tissue, in which the loss of the cells from the surface of the SC (desquamation) is balanced by cell growth in the lower epidermis. Upon leaving the basal layer, keratinocytes begin to differentiate and during their apical migration through the stratum spinosum and stratum granulosum (SG), they undergo a number of changes in both structure and composition. The keratinocytes synthesize and express numerous different structural proteins and lipids during their maturation. The final steps in keratinocyte differentiation are associated with profound changes in their structure resulting in their transformation into corneocytes. The corneocytes are relatively flat, anucleated squamous cells packed mainly with keratin filaments, and surrounded by a cell envelope composed of cross-linked proteins, as well as a covalently bound lipid (CLE) envelope. This corneocyte lipid envelope most probably plays an important role in keeping the osmotically active material inside the corneocytes. Extracellular non-polar lipids surround the corneocytes, forming a hydrophobic

matrix. Furthermore, corneodesmosomes interconnect adjacent corneocytes and are important for the SC cohesion.