Roles of Lipids in the Permeability Barriers of Skin and Oral Mucosa

Abstract

PubMed searches reveal much literature regarding lipids in barrier function of skin and less literature on lipids in barrier function of the oral mucosa. In terrestrial mammals, birds, and reptiles, the skin's permeability barrier is provided by ceramides, fatty acids, and cholesterol in the outermost layers of the epidermis, the stratum corneum. This layer consists of about 10-20 layers of cornified cells embedded in a lipid matrix. It effectively prevents loss of water and electrolytes from the underlying tissue, and it limits the penetration of potentially harmful substances from the environment. In the oral cavity, the regions of the gingiva and hard palate are covered by keratinized epithelia that much resemble the epidermis. The oral stratum corneum contains a lipid mixture similar to that in the epidermal stratum corneum but in lower amounts and is accordingly more permeable. The superficial regions of the nonkeratinized oral epithelia also provide a permeability barrier. These epithelial regions do contain ceramides, cholesterol, and free fatty acids, which may underlie barrier function. The oral epithelial permeability barriers primarily protect the underlying tissue by preventing the penetration of potentially toxic substances, including microbial products. Transdermal drug delivery, buccal absorption, and lipid-related disease are discussed.

Keywords: barrier function; ceramides; cholesterol; fatty acids; intercellular lamellae; keratinocytes; oral mucosa; skin.

Figure 1

The linoleate-rich acylglucosylceramide (center) is the precursor of the linoleate-rich acylceramide (bottom) found in the intercellular spaces of the stratum corneum and the covalently bound ω-hydroxyceramide (top), or CLE.

Figure 2

Transmission electron micrograph of RuO₄-fixed human stratum corneum showing intercellular lamellae between two corneocytes (SC). The first lucent band on either side of the intercellular space is the CLE. Bar = 50 nm.

Figure 3

Structures of ceramides from human stratum corneum [47]. In the nomenclature on the left S, P, and H indicate sphingosine, phytosphingosine and 6-hydroxysphingosine, and N, A, and O indicate normal fatty acid, α-hydroxyacid and ω-hydroxyacid. E indicates the presence of an ester-linked fatty acid [48]. In these structures, sphingosine is always accompanied by dihydrosphingosine. The numbers on the right indicate the ceramides found in the porcine stratum corneum [26]. In this case, CER AS (4/5) separates into two fractions on thin-layer chromatography. Fraction 4 contained mainly C24–C28 α-hydroxyacids, while fraction 5 contained α-hydroxypalmitic acid as the sole amide-linked fatty acid.

Figure 4

Transmission electron micrograph of RuO4-fixed superficial porcine epithelium from the floor of the mouth. The arrow indicates the plasma membrane. The double arrows indicate a stack of lamellae running transversely across the intercellular space. The magnification was ×100,000. Reprinted with permission from ref. [53]. Copyright 1995 Elsevier.