Stratum corneum composition

Other than possibly for the insensible perspiration they absorb, transdermal patches tend to operate as thermodynamically static systems, meaning as com-positionally fixed systems, from the moment they are applied until their removal. Marketed ethanol-driven estradiol and fentanyl patches are exceptions because they meter out ethanol and drive it into the stratum corneum to propel the absorption process. Compositional steadfastness is still the rule, however, and it is this feature that bestows the zero-order delivery attribute on the ordinary transdermal patch. Drug is present within the patches in reservoir amounts whether or not the reservoir compartment is easily distinguished, for there must be enough drug to sustain delivery over the full course of patch wear. 

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],... 

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). 

M. W. De Jager, G. S. Gooris, I. P. Dolbnya, M. Ponec, and J. A. Bouwstra. Modelling the stratum corneum lipid organisation with synthetic lipid mixtures The importance of synthetic ceramide composition. Biochim. Biophys. Acta Bio-membr. 1664 132-140 (2004). 

K. Miyajima, S. Tanikawa, M. Asano, and K. Matsuzaki. Effects of absorption enhancers and lipid composition on drug permeability through the model membrane using stratum corneum lipids. Chem. Pharm. Bull. 42 1345-1347 (1994). 

As an emollient, squalene is expected to increase skin hydration due to skin surface occlusions. In addition, squalene is a substance believed to maintain moisture in the stratum corneum. Novel substitutes were researched for vernix caseosa which is a reported highly efficient barrier cream for facilitating stratum corneum hydration for barrier-deficient skins. For this purpose, various lipid fractions were mixed with squalene, triglycerides, cholesterol, ceramides, and fatty acids to produce a mixture that can generate similar compositions of vernix caseosa (Rissmann et ah,... 

Microscopically, the skin is a multilayered organ composed of many histological layers. It is generally subdivided into three layers the epidermis, the dermis, and the hypodermis [1]. The uppermost nonviable layer of the epidermis, the stratum corneum, has been demonstrated to constitute the principal barrier to percutaneous penetration [2,3]. The excellent barrier properties of the stratum corneum can be ascribed to its unique structure and composition. The viable epidermis is situated beneath the stratum corneum and responsible for the generation of the stratum corneum. The dermis is directly adjacent to the epidermis and composed of a matrix of connective tissue, which renders the skin its elasticity and resistance to deformation. The blood vessels that are present in the dermis provide the skin with nutrients and oxygen [1]. The hypodermis or subcutaneous fat tissue is the lowermost layer of the skin. It supports the dermis and epidermis and provides thermal isolation and mechanical protection of the body. 

In the first part of this chapter, the formation and structure of the stratum corneum will be discussed. The second part describes the composition and organization of the intercellular stratum corneum lipids in vivo and in vitro. 

The lipid composition changes dramatically during terminal differentiation. After extrusion from the lamellar bodies, the polar lipid precursors are enzymatically converted into more hydrophobic lipids. As a result, phospholipids are almost absent in the stratum corneum. The lipid lamellae surrounding the corneocytes are predominantly composed of ceramides, cholesterol, and free fatty acids. It is generally assumed that these lipids are present in nearly equimolar ratios. However, inspection of literature data shows that there is a high interindividual variability in the lipid composition [37],... 

The composition of the free fatty acids is also unique. In both human and pig stratum cornea, the free fatty acid fraction consists mainly of long and saturated hydrocarbon chains [44,45], Oleic and linoleic acid are the only unsaturated free fatty acids detected in the stratum corneum. There are various sterols present in human stratum corneum, of which cholesterol predominates. Cholesterol is the only major lipid class that is present in both plasma membranes and the intercellular lipid lamellae. Cholesterol is synthesized in the epidermis and this synthesis is independent of the hepatic one. A minor fraction is sulfated to... 

Altered Lipid Composition and Organization in Stratum Corneum of Diseased and Dry Skin... 

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. 

The above results demonstrate that the unique stratum corneum lipid organization can be reproduced in vitro with mixtures based on cholesterol, free fatty acids, and a limited number of synthetic ceramides. The results further reveal that the formation of the LPP is rather insensitive toward changes in the total composition of cholesterol, CER, and free fatty acids over a wide range of molar ratios. This is in excellent agreement with the in vivo situation, in which a high interindividual variability in stratum corneum lipid composition usually does not lead to substantial changes in the lipid organization. 

Wertz, P.W., et al. 1985. The composition of the ceramides from human stratum corneum and from comedones. J Invest Dermatol 84 410. 

Rawlings, A.Y., et al. 1994. Abnormalities in stratum corneum structure, lipid composition, and desmosome degradation in soap-induced winter xerosis. J Soc Cosmet Chem 45 203. 

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. 

Some data indicates that there is a change in composition and arrangement of the lipids during the transition through stratum corneum.30,31 This can in part depend on the presence of lipids from sebum secretion. Together with the decrease in water across stratum corneum it is possible that there is a rearrangement of the lipid structure, which in turn can be of importance for the desquamation process. 

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. 

The lipid bilayers of the stratum corneum not only constitute a barrier, but may also function as a pool from which substances can slowly penetrate into the system on a downhill gradient. The actual effect of solvents and detergents on barrier lipid structure is not known in any satisfactory detail. Likewise, we are only starting to understand how different moisturizers might influence the structure and function of the barrier. We still lack an understanding of how the composition of the ceramide, FFA, and cholesterol influences the defect barrier in some pathological disorders, for example, dry atopic skin. 

Wertz, P.W. and Norlen, L., Confidence Intervals for the true hpid composition of the human stratum corneum, in Skin, Hair, andNails—Structure and Function, Forshnd, B., Lindberg, M., and Norlen, L., Eds., Marcel Dekker, New York, 2004, pp. 85-106. 

The elucidation of the molecular genetics RXI has had a major impact on our understanding of stratum corneum turnover. Individuals with RXI lack an enzyme, cholesterol sulfatase,3,4 which catalyzes the transformation of cholesterol sulfate (CS) to cholesterol and free sulfate. As a result there is an accumulation of CS in the stratum corneum intercellular space. Possible mechanisms by which this change in intercellular lipid composition of the stratum corneum can cause disturbances in desquamation, leading to ichthyosis, will be discussed later. 

There are a vast number of other factors which may be expected to influence the rate of desquamation, for instance, by affecting the rate of proteolytic reactions. pH, water, and ion concentrations, and lipid composition may all be expected to be of importance. Experimental data in this area are very scarce, but some speculations can be made. For instance, the pH dependency of SCCE activity could be of importance. SCCE has optimal activity at pH 7 to 8, but close to half its maximal activity at pH 5.5.36,37 This implies that rather small variations in either direction of the pH of the extracellular space should have effects on the rate of SCCE-mediated protein degradation. In support of this, the rate of spontaneous cell dissociation observed in plantar stratum corneum in vitro showed a marked pH dependency, being highest at neutral to weakly alkaline pH and decreasing at lower pH values.10... 

The composition of the stratum corneum intercellular lipids may have profound effects on desquamation. In addition to modifying effects on, for example, proteolytic enzymes and their substrates,34 lipids may also be directly involved in corneocyte cohesion. The effects of cholesterol sulfate have already been mentioned. In addition to RXI, there are a number of other hereditary diseases with disorders of desquamation associated with disturbances in lipid metabolism. Furthermore, scaling as a result of treatment with lipid-lowering drugs has been observed (for review, see References 1 and 2). 

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