Stratum lipid

Sodium dodecyl sulfate has been used to induce a dry, scaly skin condition in human subjects by daily treatment with a 4% aqueous solution on one leg over a period of 2 weeks. Measurements were made of stratum comeum hydration, scaliness, and lipid composition which were used to assess in vivo surfactant perturbations on desquamation [381]. 

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]. 

Salicylic acid (ortho hydroxybenzoic add) is a beta hydroxy acid agent. It is a lipophilic compound which produces desquamation of the stratum corneum via removal of intercellular lipids [3] (see salicylic acid section). Given its keratolytic effects, it has become an increasingly popular superficial peeling agent. Salicylic acid peels induce injury via thinning or removal of the stratum corneum. In addition, salicylic acid potentially enhances the penetration of TCA. 

A study using skin samples from healthy humans revealed that trichloroethylene extracts lipids from the stratum comeum (Goldsmith et al. 1988). The study indicates that lipid extraction is the reason for whitened skin following exposure to solvents such as trichloroethylene. 

Goldsmith LB, Friberg SE, Wahlberg JE. 1988. The effect of solvent extraction on the lipids of the stratum comeum in relation to observed immediate whitening of the skin. Contact Dermatitis 19 348-350. 

Raith and Neubert [57] have developed a method for the profihng of human stratum comeum ceramides. The method enables the investigation of the role of ceramides in maintaining the barrier function of stratum comeum. TLC using automated multiple development was modified for semipreparative purposes. The fractionation of complex lipid extracts using this method ensured specific, sensitive, and... 

In addition, data obtained from infrared, thermal, and fluorescence spectroscopic studies of the outermost layer of skin, stratum corneum (SC), and its components imply enhancer-improved permeation of solutes through the SC is associated with alterations involving the hydrocarbon chains of the SC lipid components. Data obtained from electron microscopy and x-ray diffraction reveals that the disordering of the lamellar packing is also an important mechanism for increased permeation of drugs induced by penetration enhancers (for a recent review, see Ref. 206). 

Although much is still to be learned about the factors that contribute to the pliability of the stratum corneum, it is generally accepted that its elasticity is dependent on a proper balance of lipids, hygroscopic,... 

Skin toxicity is determined by the penetration and transport of the compound being tested through the lipid matrix in the outer skin layers (the stratum corneum)... 

The homy layer consists of about 10% extracellular components such as lipids, proteins, and mucopolysaccharides. Around 5% of the protein and lipids form the cell wall. The majority of the remainder is present in the highly organized cell contents, predominantly as keratin fibers, which are generally assigned an a-helical structure. They are embedded in a sulphur-rich amorphous matrix, enclosed by lipids that probably he perpendicular to the protein axis. Since the stratum comeum is able to take up considerably more water than the amount that corresponds to its volume, it is assumed that this absorbed fluid volume is mainly located in the region of these keratin structures. 

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. 

The nails are composed of flattened, keratinized cells, fused into a dense and hard, yet slightly elastic plate. Their thickness varies from 0.5 to 1.0 mm. In contrast to the stratum corneum (10%), the total lipid content of the nails lies between 0.1% and 1%, and the keratin domain is harder, due to higher sulfur content (cystine). Moreover, the water content is only 7% to 12%, in comparison to 25% in the stratum corneum. The relative water gain may not exceed 25% at 100% relative humidity, in sharp contrast to 200-300% as found in the stratum corneum. 

The intercellular route is considered to be the predominantly used pathway in most cases, especially when steady-state conditions in the stratum corneum are reached. In case of intercellular absorption, substance transport occurs in the bilayer-structured, continuous, intercellular lipid domain within the stratum corneum. Although this pathway is very tortuous and therefore much longer in distance than the overall thickness of the stratum corneum, the intercellular route is considered to yield much faster absorption due to the high diffusion coefficient of most drugs within the lipid bilayer. Resulting from the bilayer structure, the intercellular pathway provides hydrophilic and lipophilic regions, allowing more hydrophilic substances to use the hydrophilic and more lipophilic substances to use the lipophilic route. In addition, it is possible to influence this pathway by certain excipients in the formulation. 

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. 

Of particular interest are membranes prepared of an inert porous support carrying natural or artificial lipids. These coatings may comprise a single component, such as isopropylmyristate or dodecanol [99, 106], or mixtures of comparable composition as the stratum corneum intercellular bilayer [107, 108], Usually, synthetic lipids are used, due to an elaborate isolation procedure for stratum corneum lipids, with limited yield and the necessity of separation of triglycerides, originating from subcutaneous fatty tissue or skin care products [109],... 

A. P. M. Lavrijsen, J. A. Bouwstra, G. S. Gooris, A. Weerheim, H. E. Bodde, and M. Ponec. Reduced skin barrier function parallels abnormal stratum comeum lipid organization in patients with lamellar ichthyosis. J. Invest. Dermatol. 105 619-624 (1995). 

P. M. Elias, E. R. Cooper, A. Korc, and B. E. Brown. Percutaneous transport in relation to stratum corneum structure and lipid composition. J. Invest. Dermatol. 76 297-301 (1981). 

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). 

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