ABSTRACT

ModelsFrom a biological point of view, skin has two layers: epidermis and dermis. However, from a morphological or transport perspective, three layers must be distinguished: stratum corneum, viable epidermis, and dermis. Each of these layers is discussed briefly in the following text. One must also recognize that human skin is pierced with three types of appendages: hair follicles and their associated sebaceous glands (pilosebaceous units), eccrine sweat glands, and apocrine sweat glands. The nature and density of these appendages vary sharply with body site. This review will not specifically address skin appendages other than to note that they are important for the transport of hydrophilic solutes [5] and, possibly, for all solutes at short times [1,2,7,8]. They are often described in terms of a “porous” or “polar” pathway through the stratum corneum [9-12]. An as-yet-unpublished microscopic transport model of the hair follicle is also available for study [13]. 7.2.1 Stratum CorneumIt has been recognized for some time that the composite nature of the stratum corneum, with dried, cornified cells (corneocytes) interspersed in a matrix of structured lipids [4,14-16], is responsible for its remarkable barrier function (Fig. 7.1). However, the precise contribution of each component to the barrier and the associated

possibilities for transport pathways has been the subject of a longstanding debate. The term “bricks-and-mortar” [4] combined with early observations that lipophilic permeants and even some putative hydrophilic ones [17] were generally found in intercellular spaces prompted many workers to conclude that the corneocytes were effectively impermeable to most solutes. However, others have noted that water swells corneocytes [18-21] and amino acids and other natural moisturizing factor components are depleted from the outer stratum corneum layers by washing [22]. Recent twophoton fluorescence microscopy studies also support the presence of diffusible solutes within corneocytes [23].