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The skin barrier is a watertight seal around the keratinocytes in the upper levels of the epidermis. It prevents evaporation of water from the surface of the skin, which is known as transepidermal water loss (TEWL). It is important to note that TEWL is not the same as sweating or perspiration. Increased TEWL occurs when a defect in the permeability barrier allows excessive water to be lost to the atmosphere. The skin barrier decreases TEWL and helps keep unwanted compounds out of the skin, such as allergens and irritants. Skin with an injured barrier is more susceptible to contact and irritant dermatitis as well as infection. Skin barrier perturbation can be caused by many different factors such as detergents, acetone, friction, ultraviolet exposure, prolonged or frequent water immersion, cholesterol-lowering drugs, low-fat diets, and genetic predisposition (e.g., to disorders of filaggrin).

The extracellular lipid mixture surrounding keratinocytes in the upper layer of the epidermis (stratum corneum or SC) is well known to be responsible for that layer’s water barrier function.1 This lipid mixture, which is synthesized by lamellar bodies in the lower levels of the epidermis, is composed of 50 percent ceramides, about 25 percent cholesterol, and about 15 percent fatty acids.2 Many studies have considered the effect of topically applying these important skin barrier lipids to improve skin barrier function and, thus, skin hydration. These investigations have demonstrated that the exogenously applied lipids must be in the proper ratio to form the correct three-dimensional structure of the skin barrier. When the correct ratios of ceramides, fatty acids, and cholesterol were used, the barrier recovered.3 Application of a mixture of cholesterol, ceramides, and the essential/nonessential free fatty acids palmitate and linoleate in an equimolar ratio allows normal barrier recovery, whereas a 3:1:1:1 ratio of these four ingredients accelerates barrier recovery.4 Today, the goal of the best barrier repair moisturizers is to provide these vital components in a 3:1:1:1 ratio.


Older skin displays increased drug penetration, dryness, and other signs that the skin barrier may be impaired. Ghadially et al. showed that although the composition, dimensions, and lamellar structure of the bilayer lipids were normal in older individuals (80+ years), their skin had 30 percent less lipids than younger people (20–30 years old) and the number of focal SC lamellar bilayers was decreased. In addition, the barrier recovery time was much longer in older individuals.5 Waller and Maibach reviewed studies on lipids in aged skin and deemed the findings to be conflicting, with no consensus on whether or not older skin displays a different lipid composition as compared to younger skin.6


Topically applied lipids are transported to the nucleated layers of the SC (such as the spinous layer), internalized, and transported to the distal Golgi apparatus where they are incorporated ...

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