Stratum corneum barrier lipids

STRATUM CORNEUM BARRIER LIPIDS 11.3.1 Penetration Pathway through the Stratum Corneum... 

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. 

There are several genetic skin diseases with known defects in the lipid metabolism. Atopic dermatitis, lamellar ichthyosis, and psoriasis have been the most widely studied with respect to epidermal barrier function and alterations in the lipid profile. Deviations in the lipid profile have been linked with an impaired stratum corneum barrier function. Atopic dermatitis is characterized by inflammatory, dry and easily irritable skin, and overall reduced ceramide levels in the stratum corneum [58-60]. In particular a significant decrease in the ceramide 1 level is observed, whereas the levels of oleate that is esterified to ceramide 1 are elevated [59]. Both aberrations may be responsible for the reduced order of the lamellar phases as observed with freeze fracture electron microscopy [61]. It has further been established that, in comparison to healthy stratum corneum, the fraction of lipids forming a hexagonal packing is increased [61]. A recent study reveals that the level of free fatty acids... 

All the above-mentioned changes in lipid composition and organization in diseased and dry skin likely contribute to an impaired stratum corneum barrier function and increased susceptibility to dry skin. However, as previously indicated, abnormalities in the process of envelope formation may also strongly influence the stratum corneum barrier integrity. Therefore, more information is required to elucidate the precise mechanisms by which stratum corneum structure and function are altered. 

To further increase our insight into the stratum corneum barrier function, stratum corneum lipid models have been developed. The main advantage of these lipid models is that the... 

Dermal and transdermal delivery requires efficient penetration of compounds through the skin barrier, the bilayer domains of intercellular lipid matrices, and keratin bundles in the stratum corneum (SC). Lipid vesicular systems are a recognized mode of enhanced delivery of drugs into and through the skin. However, it is noteworthy that not every lipid vesicular system has the adequate characteristics to enhance skin membrane permeation. Specially designed lipid vesicles in contrast to classic liposomal compositions could achieve this goal. This chapter describes the structure, main physicochemical characteristics, and mechanism of action of prominent vesicular carriers in this field and reviews reported data on their enhanced delivery performance. 

Figure 1 Schematic presentation of the skin barrier (stratum corneum). The lipids are organized in crystalline lamellar packing. The repeat distances (d) of the two lamellar phases are 6 and 13 nm, respectively. 

As a generalization, we may be allowed to state that the transition temperature for cell membranes in biological living systems is found between 0 and 40°C and the chain lengths are between 16 and 18 carbons. This is in conspicuous contrast to the lipids of the stratum corneum barrier where chain lengths up to and over 30 carbons have been demonstrated.14,19 From such facts we expect the transition temperature of the skin barrier lipids to be around 40°C, and this has also been substantiated in a number of investigations.20-22 This means that under normal conditions with a skin temperature about 30°C, the barrier will essentially be impermeable to water. 

Rawlings, A.V. etal. Keratinocyte ceramide synthesis, effect of lactic acid isomers on stratum corneum lipid levels and stratum corneum barrier function, Arch. Dermatol. Res., 288, 383, 1996. 

Permeability changes in full-thickness skin have been associated with temperature or solvent pretreatment. The molecular basis of these permeability changes has been attributed to lipid melting or protein conformational changes. The current studies have probed the role of lipid fluidity in the permeability of lipophilic solutes, and examined the effects of temperature on the physical nature of the stratum corneum by differential scanning calorimetry and thermal perturbation infrared spectroscopy. Combining molecular level studies that probe the physical nature of the stratum corneum with permeability results, a correlation between flux of lipophilic solutes and nature of the stratum corneum barrier emerges. 

Bouwstra, J.A. Bodde, H.E. Human stratum corneum barrier impairment by iV-alkylazacycloheptanones a mechanistic study of drug flux enhancement, Azone mobility and protein and lipid perturbation. In Percutaneous Penetration Enhancers Smith, E.W., Maibach, H.I., Eds. CRC Press Boca Raton, Florida, 1995 137-169. 

The cornified cell envelope is the outermost layer of a corneocyte, and mainly consists of tightly bundled keratin filaments aligned parallel to the main face of the corneocyte. The envelope consists of both protein and lipid components in that the lipid is attached covalently to the protein envelope. The envelope lies adjacent to the interior surface of the plasma membrane. " The corneocyte protein envelope appears to play an important role in the structural assembly of the intercellular lipid lamellae of the stratum corneum. The corneocyte possesses a chemically bound lipid envelope comprised of A-co-hydroxyceramides, which are ester linked to the numerous glutamate side chains provided possibly by both the ot-helical conformation and p-sheet conformation of involucrin in the envelope protein matrix. In the absence of A-oo-hydro-xyceramides, the stratum corneum intercellular lipid lamellae were abnormal and permeability barrier function was disrupted. 

Liposomes with compositions that imitate the skin s lipid content (ceramides, cholesterol, fatty acids, cholesterol sulfate) have also been prepared [37] and their pharmacological response on a skin barrier disruption model was assessed. Apart from their action as lipidic carriers for the repair of skin barrier, tliese liposomes are expected to penetrate easily the skin barrier due to their biocompatibilily with the stratum corneum. Many attempts have being made to incorporate ceramides, the major component of stratum corneum. These lipids have a relatively large stereochemical shape, and in the presence of water they tend to form multilamellar bilayers [50-53],... 

There is today a consensus about penetration pathways through the skin barrier (Bodde et al. 1990). Under normal conditions, the corneocytes are permeable essentially only to water, which implies that the transport route for hydrophilic and hydrophobic substances is via the extracellular space of the stratum corneum. The lipids of this space are organised in bilayers stacked on top of each other. The corneocyte envelopes have long-chain ceramides covalently bound to their surfaces... 

SuginoK, Imokawa G, Maibach HI (1993) Ethnic differences of skin lipids in relation to stratum corneum barrier function. J Invest Dermatol 100 587... 

Rawlings AV, Davies A, Carlomusto M, Pillai S, Zhang K, Kosturko R, Verdejo P, Feinberg C, Nguyen L, Chandar P (1996) Effect of lactic acid isomers on keratinocyte ceramide synthesis, stratum corneum lipid levels and stratum corneum barrier function. Arch Dermatol Res 288 383-390 Reed JT, Ghadially R, Elias PM (1995) Skin type, but neither race nor gender, influence epidermal permeability barrier recovery. Arch Dermatol 131 1134-1138... 

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. 

T. Kai, T. Isami, Y. Kurosaki, T. Nakayama, and T. Kimura. Keratinized epithelial transport of beta-blocking agents. II. Evaluation of barrier property of stratum corneum by using model lipid systems. Biol. Pharm. Bull. 16 284—287 (1993). 

R. Lange-Lieckfeldt and G. Lee. Use of a model lipid matrix to demonstrate the dependence of the stratum corneum s barrier properties on its internal geometry. J. Control. Release 20 183-194 (1992). 

The success of the Potts-Guy equation led many authors to advocate a single mechanism as the rate determining step for permeation through the skin barrier for all or at least a wide range of solutes diffusion was assumed to occur primarily via the interkeratinocyte lipids of the stratum corneum, a mixture of ceramides, fatty acids, and sterols. While from a macroscopic point of view these lipids may be modeled as a bulk solvent, on a microscopic scale they... 

The skin barrier properties and effect of hand hygiene practices are known to be important in protecting the body. The average adult has a skin area of about 1.75 m2. The superficial part of the skin, the epidermis, has five layers. The stratum corneum, the outermost layer, is composed of flattened dead cells (comeocytes or squames) attached to each other to form a tough, homy layer of keratin mixed with several lipids, which help maintain the hydration, pliability, and barrier effectiveness of the skin. This part of skin has been compared to a wall of bricks (comeocytes) and mortar (lipids) and serves as the primary protective barrier. Approximately 15 layers make up the stratum corneum, which is completely replaced every 2 weeks a new layer is formed almost daily. From healthy skin, approximately 107 particles are disseminated into the air each day, and 10% of these skin squames contain viable bacteria. This is a source of major dirt inside the house and contributes to many interactions. 

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