j. Soc. Cosmet. Chem., 47, 27-39 (January/February 1996) The effect of lipids, with and without humectant, on skin xerosis ROBERT S. SUMMERS, BEVERLY SUMMERS, PREM CHANDAR, CAROL FEINBERG, RICHARD GURSKY, and ANTHONY V. RAWLINGS, School of Pharmacy, Medical University of South Africa, P.O. Box 218, Medunsa 0204, South Africa (R. S. S., B. S. ), and Unilever Research US Inc., Edgewater, N.J. 07020 (P. C., C. F., R. G., A. V. R.). Received August 1995. Presented in part at the Society for Investigative Dermatology, April 1995 Synopsis Specialized lipids found in the stratum corneum, namely ceramides, have been shown to have beneficial skin properties due to their lipid bilayer-forming potential in the presence of cholesterol and fatty acids. We were interested in determining whether other bilayer-forming lipids, such as phospholipids, could deliver similar benefits and how these benefits compare with common moisturizer ingredients such as petrolatum and glycerol. We investigated a bilayer-forming mixture of phospholipids, cholesterol, and fatty acid for its effectiveness in treating soap-induced winter xerosis in double-blind, fully randomized clinical trials in which dryness on the dorsal aspect of the hands was visually assessed using a seven-point grading scale. Sixty-six healthy Caucasian women aged over 25 underwent a one-week soap "dry-down" and were treated for two weeks with twice-daily product applications in balanced treatment groups (N = 11). Treatments were compared statistically using repeated Wilcoxon rank sum tests (critical significance level of 5%). Examination of improvements in xerosis in vivo established that emulsions of phospholipids, cholesterol, and stearic acid alone, or thickened solutions of glycerol alone, did little to alleviate skin xerosis. When lipids and glycerol were combined, however, the emulsions acted in a synergistic way and reduced skin xerosis significantly and rapidly. In contrast, when phospholipids were replaced with petrolatum in the emulsions, the rate of xerosis alleviation was reduced, which implies that the bilayer-forming capabilities of phospho- lipids may be important in delivering optimal skin benefit. These studies demonstrate that lipids with bilayer-forming capabilities such as phospholipids can rapidly alleviate skin xerosis when combined with glycerol. INTRODUCTION Stratum corneum moisturization is essential for the normal functioning of the skin. The degree of moisturization depends directly on the inherent humetancy properties of the stratum corneum and on its water barrier function (for review, see reference 1). The structure of stratum corneum and its lipid content, probably both intercellular and covalently bound to corneocytes, affect barrier function (2-4). The lipids consist mainly of ceramides, cholesterol, and fatty acids the total and respective levels of these are 27

28 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS influenced by diet, age, race, environment (and seasons), and certain skin conditions (5-7). In psoriasis, for example, stratum corneum cholesterol levels are raised and fatty acids and ceramides decreased, compared with normal subjects (8). The composition of covalently bound lipids in psoriatic stratum corneum also differs from that of healthy stratum comeurn (9). In atopic dermatitis, stratum comeurn ceramide levels, particu- larly ceramide one-linoleate levels, are particularly low (10, 11). Changes in stratum corneum lipid levels are also associated with several hereditary disorders (12), the best-described of which is recessive X-linked ichthyosis (RXLI), in which there is a specific abnormality in sterol metabolism (12), which leads to excessively high levels of cholesterol sulphate in the stratum corneum. Deterioration in skin condition due to seasonal changes in the weather affects far more people than all the above conditions combined, and it is only recently that we have begun to understand the reasons for this situation. Seasonal changes in lipid levels and types occur, with reductions in their levels in winter compared with those in summer (7). Bathing habits also influence the levels of lipids in the superficial layers of the stratum corneum. As a result, in soap-induced winter xerosis, the total levels of stratum corneum ceramides are decreased while those of fatty acids are increased in comparison with normal skin (13-15). The orderly bilayer architecture of these lipids is also dis- rupted in the superficial layers of the stratum corneum (14,15), which probably con- tributes to the increased transepidermal water loss known to occur in these conditions (16). All of these conditions are manifested as dry, flaking skin, which may be more or less severe. The underlying factor that causes the changes in skin structure, function, and appearance in skin xerosis is the failure of the normal desquamatory process, which itself depends upon the specific degradation of intercorneocyte cohesive factors (1,15). For instance, it is known that certain proteases in the stratum corneum are responsible for the normal orderly degradation of desmosomes (17, 18). It has also been reported that enzymic activity, and thereby desmosome degradation, occurs only above a certain water content in the stratum corneum (19,20). When stratum corneum lipid structure is disturbed, the resulting reduction in stratum corneum hydration leads to the retention of corneocytes on the skin's surface and the manifestation of skin xerosis due to reduced desmosome degradation. If, therefore, stratum corneum moisturization and water bar- rier function can be restored by the topical use of suitable lipids and humectants, the desquamatory process may be normalized and xerotic skin conditions may be treated more effectively than they are at present. One compound that is widely recognized for its importance in skin care products is glycerol (21). Products containing glycerol have been shown to be very effective in the treatment of skin xerosis (22), and the action of glycerol has been explained in terms of its occlusive (23), humectant (23,24), and lipid-phase modulating (25,26) properties, all of which translate into moisturization and barrier improvements for the stratum corneum. More recently we have demonstrated that glycerol aids the enzyme lysis of desmosomes in the stratum corneum (19,20). Other occlusive agents also assist to maintain stratum corneum barrier function and improve skin condition. Recently, petrolatum has been shown to penetrate the stratum corneum and interact with stratum corneum lipids (27). Also, stratum corneum ceramides themselves applied topically, particularly in combination with cholesterol and fatty acids, have also been shown to be effective in restoring barrier function in mice with perturbed epidermal barrier function induced by solvents (28), as well as in treating skin xerosis in humans (29,30). The