Stratum corneum intercellular lipids composition

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). 

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],... 

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. 

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 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. 

In general, rat skin has been proven more permeable than human skin (ECETOC, 1993). This is likely to be caused by the different structure of the skin in both species (e.g. number of appendages, intercellular lipid composition of the stratum corneum and corneocyte surface area). It should be noted, however, that some cases have been reported where rat skin was found to be less permeable than human skin (Hotchkiss et al., 1992). Since the availability of human skin is limited, pig skin is often used. Because of its similar morphology and barrier function (Bronaugh et al., 1982), pig skin is often considered a good alternative to human skin. 

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 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... 

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