Human stratum corneum ceramides, structures

FIGURE 3.1 Representative structures of human stratum corneum ceramides. 

FIGURE 11.2 Molecular structures of the ceramides (CER) present in human stratum corneum (a) and pig stratum corneum (b). 

The stratum corneum intercellular lipids exist as a continuous lipid phase occupying about 20% of the stratum corneum volume and arranged in multiple lamellar structures. They are composed of cholesterol (27 /o) and ceramides (41 /o), together with free fatty acids (9 /o), cholesteryl esters (10 /o) and cholesteryl sulfate (2 /o) (Table 1). Phospholipids, which dominate in the basal layer, are converted to glucosylceramides and subsequently to ceramides and free fatty acids, and are virtually absent in the outer layers of the stratum corneum. Eight classes of ceramides have been isolated and identified in human stratum corneum but the functions of the individual ceramide types are not fully understood. Similarly, the exact function of cholesterol esters within the stratum corneum lamellae is also elusive but it is theoretically possible that cholesterol esters may span adjacent bilayers and serve as additional stabilizing moieties. 

The barrier properties of human skin have long been an area of multidisciplinary research. Skin is one of the most difficult biological barriers to penetrate and traverse, primarily due to the presence of the stratum corneum. The stratum cor-neum is composed of comeocytes laid in a brick-and-mortar arrangement with layers of lipid. The corneocytes are partially dehydrated, anuclear, metabolically active cells completely filled with bundles of keratin with a thick and insoluble envelope replacing the cell membrane [29]. The primary lipids in the stratum corneum are ceramides, free sterols, free fatty acids and triglycerides [30], which form lamellar lipid sheets between the corneocytes. These unique structural features of the stratum comeum provide an excellent barrier to the penetration of most molecules, particularly large, hydrophilic molecules such as ASOs. 

The stratum corneum is the outer most layer of nonviable epidermis. It has a thickness of about 10 to 12 pm. The stratum corneum consists of 15 to 25 layers of flattened, stacked, hexagonal, and cornified cells known as corneocytes. Each cell is approximately 40 pm in diameter and 0.5 pm in thickness [Bouwstra, 1997]. The thickness of stratum corneum varies with the site of human body. The body extremities such as palms and soles have a thicker stratum corneum [Walters and Roberts, 2002]. The stratum corneum is characterized by an array of keratin-rich corneocytes surrounded by lipid lamella made of cholesterol, free fatty acids, and ceramides [Bouwstra, 1997]. The corneocytes are arranged in brick and mortar structure. Such structural arrangement creates a tortuous intercellular diffusion pathway for water or any other molecules that transverse the stratum corneum. The hydrophobic lipids that surround these diffusion paths or water pores are organized in tight lamellar structure. The summative effects translate to the formation of a tight permeation barrier [Menon, 2002]. 

Figure 12.15 Formation of the lipid barrier of human skin. The top layer of the epidermis called stratum corneum is a hornified and inert barrier. Its primary functions are regulation of the skin s moisture content and protection of the underlying tissues against external influences. Due to its structure it is often compared to a brick wall in which the non-viable keratin-filled corneocytes are embedded like bricks in a matrix of intercellular lipids. Synthesis of the stratum corneum lipids starts in deeper skin layers, where lipids (mainly glucosylceramides and sphingomyelin) are produced and packaged in so-called lamellar bodies . During differentiation and maturation, these lipids are enzymatically converted to ceramides and finally assembled into densely packed lamellar structures surrounding the corneocytes and filling the intercellular spaces of the stratum corneum.

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