Corneocytes structure

It is a lipophilic compound which removes intercellular lipids that are covalently linked to the cornified envelope surrounding epithelial cells [3]. It also enhances penetration of other agents. Resorcinol (m-dihydroxy benzene) is structurally and chemically similar to phenol. It disrupts the weak hydrogen bonds of keratin [4]. Lactic acid is an alpha hydroxy acid which causes corneocyte detachment and subsequent desquamation of the stratum corneum [5]. 

The stratum corneum consists of separated, nonviable, cornified, almost nonpermeable corneocytes embedded into a continuous lipid bilayer made of various classes of lipids, for example, ceramides, cholesterol, cholesterol esters, free fatty acids, and triglycerides [6], Structurally, this epidermis layer is best described by the so-called brick-and-mortar model [7], The stratum corneum is crucial for the barrier function of the skin, controlling percutaneous absorption of dermally applied substances and regulating fluid homeostasis. The thickness of the stratum corneum is usually 10-25 /an, with exceptions at the soles of the feet and the palms, and swells several-fold when hydrated. All components of the stratum corneum originate from the basal layer of the epidermis, the stratum germinativum. 

Under normal conditions, the transcellular route is not considered as the preferred way of dermal invasion, the reason being the very low permeability through the corneocytes and the obligation to partition several times from the more hydrophilic corneocytes into the lipid intercellular layers in the stratum corneum and vice versa. The transcellular pathway can gain in importance when a penetration enhancer is used, for example, urea, which increases the permeability of the corneocytes by altering the keratin structure. 

FIGURE 2.2 A diagram of human skin. Epidermal thickness depends upon body site being thickest on the palms and soles (-1500 pm) and thinnest around the eyes (-10 pm). The stratum corneum is the only layer composed of anucleated, terminally differentiated kerati-nocyte cells called corneocytes. All other epidermal layers contain nucleated keratinocytes. The dermis is composed primarily of the structural proteins collagen and elastin. 

The outermost layer of the skin, the cornified layer or stratum corneum, has been identified as the principal diffusion barrier for substances, including water [2,3]. It is approximately 10 to 20 pm thick when dry but swells to several times this thickness when fully hydrated [17], It contains 10 to 25 layers lying parallel to the skin surface of nonviable cells, the corneocytes, which are surrounded by a cell envelope and imbedded in a lipid matrix. This architecture is often modeled as a wall-like structure, with the corneocytes as protein bricks embedded in a lipid mortar [18]. Similarly to the viable epidermis, desmosomes (corneodesmosomes) contribute to the cell cohesion. 

A number of works investigated the interaction between niosomes and human skin. With niosomes prepared from Ci2 alcohol polyoxyethylene ether and cholesterol, vesicular structures of about 100 nm size have been observed between the first and second layers of human corneocytes 48 h after incubation as well as in the deeper strata of the skin [37], The authors concluded that the structures visualized in the deeper regions could be vesicles reorganized from individual molecules that penetrated the skin. In another study, electron micrographs illustrated that niosomes containing surfactants and cholesterol affected only the most superficial corneocytes. Moreover, two-photon fluorescence microscopy confirmed that fluorescent probe encapsulated in niosomes was confined to the intercellular spaces within the apical stratum corneum layers [56]. 

Although the DMSO intensity apparently parallels that of the bands derived from protein, it is not necessarily correct to conclude that DMSO is excluded from lipid containing regions, since the area around the corneocytes is surrounded by lipidic structures that are of a spatial dimension much smaller than the spatial resolution of the current IR experiment. However, the ability of IR imaging to track the permeation of exogenous materials is clearly demonstrated. 

Figure 4 Nat 106 liposomes have a strong effect on the microstructure of the stratum corneum. The corneocytes (C) were swollen considerably, and the smooth ultrastructure of the intercellular lipid lamellae showed flattened spherical structures (see arrows). The linear arranged keratin filaments along the cell boundary of the corneocytes are absent. The scale bar indicates 0.1 pm. 

Figure 9 Freeze-fracture electron microscopy of control (a) or after treatment of alkyl-azones (b-f). (b) Hexyl-azone (c) octyl-azone (d) dodecyl-azone (e) myristyl-azone and (f) oleyl-azone. Bar represents 100 nm. represents rough structures indicating either separate domains of enhancer or more perturbation of lipid lamellae. Arrows indicate a clear presentation of the intact smooth regions of intact lamellae with steps (fracture across the lamellae). C, Corneocyte scl, stratum corneum lipid lamellae. 

S. H. White, D. Mirejovsky, and G. I. King, Structure of lamellar lipid domains and corneocyte envelopes of murine stratum corneum. An X-ray diffraction study,... 

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. 

FIGURE 2.2 (a) The corneocyte is a flat, hexagonal-like structure with a surface area of about 1000 /zm2 and... 

In 1975, Michaels et al.33 presented a conceptual model of the arrangement of corneocytes and lipids in stratum corneum. They envisaged stratum corneum as a brick and mortar structure with the keratin filled corneocytes as bricks and the intercellular lipids as mortar. This model was further explored by Elias and co-worker.34-37 This model does not per se include a structure-function perspective on the barrier but has had a tremendous impact on the research on stratum corneum and its composition, function, and the regulation of homeostasis. 

In 1994 Forslind presented a more structure-function orientated model, the domain mosaic model.38 With the background given previously, the requirements on the stratum corneum barrier can be summarized as follows the barrier should be watertight but still allow a small, controlled amount of water to leak from the system in order to keep the corneocyte keratin hydrated. 

In order to maintain water effectively within the skin the epidermis undergoes a process of maturation or terminal differentiation to produce a thin, metabolically inert, barrier, the SC. This heterogeneous structure has been likened to a brick wall in which the anucleated nonviable cells, termed corneocytes are represented as bricks embedded in a continuous matrix of specialized intercellular lipids (mortar).2 Each individual corneocyte can be viewed simplistically as a highly insoluble... 

Desquamatory proteases and other enzymes mediate their action in the lipid-rich intercellular space and need free water to be active.3 Disturbed SC lipid structure results in reduced SC hydration and retention of corneocytes on the skin surface. Subsequently skin xerosis becomes evident due to reduced desmosome degradation.5 The occurrence of dry skin associated with cold, dry weather may result from an extensive, elevated level of skin lipids in the solid state. Thereby, the material that maintains a higher proportion of lipid in the liquid crystalline state may be an effective moisturizer.6... 

Dry skin is further characterized by structural changes in comeocyte envelope (CE) as a result of reduced transglutaminase activity. The enzyme is responsible for the transformation of a soft or fragile envelope into a rigid one. Fragile corneocyte envelopes predominate in dry skin.9... 

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