Stratum intercellular lamellar

In comparison to the skin, the buccal mucosa offers higher permeability and faster onset of drug delivery, whereas the key features which help it score over the other mucosal route, the nasal delivery system, include robustness, ease of use, and avoidance of drug metabolism and degradation. The buccal mucosa and the skin have similar structures with multiple cell layers at different degrees of maturation. The buccal mucosa, however, lacks the intercellular lamellar bilayer structure found in the stratum corneum, and hence is more permeable. An additional factor contributing to the enhanced permeability is the rich blood supply in the... 

The stratum granulosum is the most superficial cell layer of the viable epidermis and contains highly differentiated keratinocytes. The lamellar bodies, which have been formed in the stratum spinosum, migrate to the apical periphery of the uppermost granular cells and eventually fuse with the membrane of the keratinocyte. Via exocytosis their content is extruded into the intercellular spaces at the stratum granulosum-stratum corneum interface. The lipids derived from the lamellar bodies are essential for the formation of the stratum corneum barrier. 

Cholesterol sulfate is another intercellular lipid. Addition of low levels of cholesterol sulfate, as observed in normal healthy stratum corneum, to lipid mixtures has little effect on the phase behavior at room temperature. However, addition of high levels of cholesterol sulfate, at levels similar to that observed in the skin disease recessive X-linked ichthyosis, promotes the formation of the long periodicity phase, induces the formation of a fluid phase, and increases the solubility of cholesterol in the lamellar phases [72,80],... 

Figure 7 The possible mechanisms involved in the effect of penetration enhancers on the lipid organization of the intercellular domains in the stratum corneum. (A) Intercalation of the enhancer in the lipid lamellae. (B) Phase separation between enhancer and skin lipids in the lamellae. (C) Phase separation between lipid lamellae and an enhancer-rich phase. (D) Intercalation of the enhancer in the lipid lamellae and simultaneous phase separation between lipid lamellae and enhancer. (E) Phase separation within the lamellae and separation between an enahncer-rich phase and the lamellar phase. (F) Disappearance of the lamellar phases.

The evolution of life in the relatively dry terrestrial environment required the development of a waterproof integument.1 In the terrestrial vertebrates, the stratum corneum provides the primary barrier to water loss. The barrier function of the stratum corneum depends upon a unique mixture of lipids that form lamellar structures in the intercellular spaces.2-5 This generally consists of ceramides, cholesterol, and long chain fatty acids. 

Ohta, N., Ban, S., Tanaka, H., Nakata, S., and Hatta, I., Swelling of intercellular lipid lamellar structure with short repeat distance in hairless mouse stratum corneum as studied by X-ray diffraction, Chem. Phys. Lipids, 123, 1, 2003. 

Figure 5 Murine stratum comeum normal full thickness. Powder diffraction patterns obtained from mouse SC at 25°C. The upper figure shows the small-angle lamellar pattern produced by the intercellular lipid domains, with a repeat period of 131 2 A. The lower figure shows the wide-angle pattern produced by the lipid alkyl chains and the comeocyte envelope. See text. (Data from White et al., 1988.)...

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 stratum corneum is the outermost layer of the epidermis and has a thickness of 10-15 pm. It is the principal barrier for the transport of most solutes (except for very lipophilic compounds) across the skin. The stratum corneum is a continuous heterogeneous structure that consists of approximately 10-25 layers of closely packed dead keratinized cells (corneocytes) cemented together by intercellular lipids. The intercellular lipids in the stratum corneum are in the form of multiple lamellar bilayers composed mainly of ceramides, cholesterol, and fatty acids. Proteins in the stratum corneum are largely concentrated within the corneocytes as keratin fibrils. The transport of lipophilic compounds across the stratum corneum is related to the intercellular lipids (lipoidal or intercellular pathways). On the other hand, it is believed that the transport of polar and ionic compounds is related to pathways with aqueous properties (the polar or pore pathways) when the stratum corneum is under a hydrated state. ... 

Figure 9.21 Bricks and mortar model of ifie stratum corneum, illustrating possible pathways of drug permeation through intact stratum corneum (transcellular and tortuous intercellular pathways) and the lamellar structure of intercellular lipids.

Moghimi H. R., Williams A. C., Barry B. W. (1996). A lamellar matrix model for stratum corneum intercellular lipids. II. Effect of geometry of the stratum corneum on permeation of model drugs 5-fluororouracil and oestradiol. 117-129. 

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]. 

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