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Keywords:

  • cleansing;
  • free fatty acids;
  • lipid bilayer;
  • stearic acid;
  • stratum corneum

Synopsis

  1. Top of page
  2. SynopsisRésumé
  3. Introduction
  4. Cellular and lipid components of the SC
  5. SC lipid formation and its composition
  6. SC lipid deficiencies in skin disorders
  7. SC lipid structure and function
  8. Cleansing-induced barrier damage
  9. Strategies for lipid management in the SC
  10. Lipid-based strategies for promoting SC barrier integrity
  11. Summary
  12. Acknowledgements
  13. References

Stratum corneum (SC) bilayer lipids, specifically fatty acids, ceramides and cholesterol, contribute to the permeability barrier function of the skin. Normal skin cleansing is associated with damage to the SC lipids because cleanser surfactants, in addition to providing the desired effect of solubilizing and facilitating the removal of sebum and skin soils, have a propensity to disrupt bilayer lipids by extracting endogenous skin lipids or intercalating into the bilayer. Disrupted SC lipids are associated with a variety of pathological skin conditions, as well as with dry skin induced by harsh cleansing. In an attempt to preserve the barrier and mitigate the damage caused by frequent normal cleansing, the incorporation of physiologically relevant lipids into skin cleansers has become common in leading cleansing products. It has been noted that fatty acids are more susceptible to surfactant-induced removal than other lipids (eg, ceramides), an observation that may form the basis for a critically important strategy for replenishing SC lipids. This review will focus on the role of fatty acids in the structure and function of the SC, and the rationale for incorporation of stearic acid into moisturizing body cleansers to minimize their extraction by surfactants and replenish lost fatty acids to promote skin barrier preservation.

Résumé

Les lipides des bicouchesdu stratum corneum (SC), les acides gras en particulier, les céramides, le cholestérol contribuent à la fonction de barrière de perméabilité de la peau. Le nettoyage normal de la peau est associé à des dommages aux lipides du SC parce que les tensioactifs nettoyants, en plus de fournir l'effet désiré de solubilisation et d'élimination du sébum et des souillures de la peau, ont une propension à perturber les lipides des bicouches par l'extraction de lipides endogènesde la peau ou ceux intercalés dans les bicouches. La perturbation des lipides du SC est associée à une variété d'affections cutanées pathologiques, ainsi qu'avec la peau sèche induite par le nettoyage agressif. Dans une tentative pour préserver la barrière et atténuer les dégâts causés par le nettoyage fréquent normal, l'incorporation de lipides physiologiquement pertinents dans les nettoyants pour la peau est devenu habituel pour les produits de nettoyage de de qualité. Il a été noté que les acides gras sont plus sensibles à l'élimination induite par les tensio-actifs que d'autres lipides (par exemple, les céramides), une observation qui pourrait constituer la base d'une stratégie cruciale pour la reconstitution des lipides du SC. Cet examen portera sur le rôle des acides gras dans la structure et la fonction du SC, et la justification de l'incorporation de l'acide stéarique dans les nettoyants hydratants pour le corps afin de minimiser leur extraction par des agents tensioactifs et de reconstituer les acides gras perdus pour promouvoir la préservation de la barrière cutanée.


Introduction

  1. Top of page
  2. SynopsisRésumé
  3. Introduction
  4. Cellular and lipid components of the SC
  5. SC lipid formation and its composition
  6. SC lipid deficiencies in skin disorders
  7. SC lipid structure and function
  8. Cleansing-induced barrier damage
  9. Strategies for lipid management in the SC
  10. Lipid-based strategies for promoting SC barrier integrity
  11. Summary
  12. Acknowledgements
  13. References

The stratum corneum (SC) plays a critical role in skin physiology, providing the functional barrier between the external environment and the deeper layers of skin, including the living dermis. An intact barrier prevents dehydration by controlling water loss to the external environment. The barrier function of the SC is also important in minimizing entry and permeation of molecules, including water molecules, into the skin from the external environment [1-4]. Generally speaking, the SC provides bidirectional permeability to control water transport, while retaining about 15% to 20% water by weight to maintain its functional properties [1-4]. It is well understood that hydration of the SC is required not only for maintaining the aesthetic properties of skin (moisturization, softness, smoothness, lack of flaking, etc.), but also for the critical processes (lipid biosynthesis, desquamation and natural moisturizing factor [NMF] production) that take place within these non-living, yet biochemically active, layers of the skin [1-4].

Cellular and lipid components of the SC

  1. Top of page
  2. SynopsisRésumé
  3. Introduction
  4. Cellular and lipid components of the SC
  5. SC lipid formation and its composition
  6. SC lipid deficiencies in skin disorders
  7. SC lipid structure and function
  8. Cleansing-induced barrier damage
  9. Strategies for lipid management in the SC
  10. Lipid-based strategies for promoting SC barrier integrity
  11. Summary
  12. Acknowledgements
  13. References

The structure of SC is generally described in terms of a ‘brick and mortar’ model in which the anucleated corneocytes (composed primarily of keratin) exist within a lipid-rich matrix containing ceramides, cholesterol, cholesterol esters and fatty acids [5]. On a weight basis, the SC contains about 70% proteins, 15% lipids and 15% water. In addition to the matrix lipids, corneocyte cells have covalently bonded lipids at the corneocyte exterior that make them compatible with the matrix lipids [6], and this exterior structure consisting of lipids covalently bonded to cross-linked proteins is referred to as the cornified lipid envelope (CLE). Inter-corneocyte adhesions are mediated by corneodesmosomes, which decline in number as the SC matures, and eventually are cleaved completely during normal desquamation [3, 5]. It is generally accepted that although the structural integrity of the SC is provided by the corneocyte bricks, other properties, such as water transport, barrier properties and the ability to accommodate and relax stress, are regulated by the intercellular lipids. Both components are critical to SC function. This review will focus on the SC lipids, particularly fatty acids (including medium-chain fatty acids, such as stearic acid), and their role in governing the properties of the SC.

SC lipid formation and its composition

  1. Top of page
  2. SynopsisRésumé
  3. Introduction
  4. Cellular and lipid components of the SC
  5. SC lipid formation and its composition
  6. SC lipid deficiencies in skin disorders
  7. SC lipid structure and function
  8. Cleansing-induced barrier damage
  9. Strategies for lipid management in the SC
  10. Lipid-based strategies for promoting SC barrier integrity
  11. Summary
  12. Acknowledgements
  13. References

The formation of SC lipids is a complex process. During keratinocyte differentiation, phospholipids, glucosylceramide, sphingomyelin and cholesterol are intracellularly packaged into lamellar bodies and then secreted into the extracellular domain of the SC [3]. Additional metabolism of these secreted lipid precursors generates an extracellular lipid matrix composed of approximately (by weight) 50% ceramides, 25% cholesterol and 15% free fatty acids, including stearic acid, with the remaining ~10% consisting of cholesterol esters [7]. Ceramides, cholesterol and fatty acids (Fig. 1) are present in approximately equimolar concentrations [8]. SC lipids are primarily non-polar and functionally distinct from a conventional phospholipid bilayer; the SC water permeability is approximately three orders of magnitude lower than for a plasma membrane [9, 10].

image

Figure 1. Molecular structures of the SC lipids: ceramides, fatty acids and cholesterol.

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Significant research conducted in recent years has increased understanding of the detailed composition and organization of SC lipids. The result has been the identification of as many as 11 subclasses of ceramides [8, 11], free fatty acids (of varying chain lengths) [12] and cholesterol [8] as the major constituents of the SC. The general consensus is that free fatty acids associated with the SC bilayer lipids are saturated with chain lengths of 16–26; however, closer to the surface, higher levels of short-chain fatty acids, including unsaturated fatty acids (C16, C18:0, C18:1 and C18:2), have been reported [8]. These short chain and unsaturated fatty acids are thought to be of sebaceous origin and can become intercalated into the SC lipids in the upper layers [12]. There has been debate as to whether C16 (palmitic) and C18 (stearic) fatty acids are of sebaceous origin or are true components of the SC. Norlen et al. [12] concluded that they are of sebaceous origin based on interpersonal variations in the level of palmitic and stearic acid. However, investigation into seasonal variations in fatty acid levels within the SC suggests that C18 fatty acids may be a part of the SC lipid fraction and not entirely of sebaceous origin. Specifically, C16 fatty acids were found to decrease in SC from summer to winter, a finding consistent with the established reductions in sebum levels observed from summer to winter. However, C18 fatty acids did not show such a corresponding decrease during the same period [13]. Irrespective of their origin, the presence of short- and medium- chain unsaturated and saturated fatty acids in the more superficial layers is of relevance from a cleansing perspective because they are regularly exposed to the external environment and daily cleansing. Cleanser surfactants have the ability to solubilize and remove these fatty acids during cleansing, which may also explain the high variability observed in Norlen et al. [12]. This aspect will be discussed further in a later section.

SC lipid deficiencies in skin disorders

  1. Top of page
  2. SynopsisRésumé
  3. Introduction
  4. Cellular and lipid components of the SC
  5. SC lipid formation and its composition
  6. SC lipid deficiencies in skin disorders
  7. SC lipid structure and function
  8. Cleansing-induced barrier damage
  9. Strategies for lipid management in the SC
  10. Lipid-based strategies for promoting SC barrier integrity
  11. Summary
  12. Acknowledgements
  13. References

Perhaps the best evidence for the important role of lipids in SC barrier function comes from research on skin conditions associated with SC lipid defects [14]. Such defects lead to clinical disorders such as atopic dermatitis (AD) or eczema, and are characterized by a compromised skin barrier and varying degrees of pruritus and xerosis [14]. Although loss-of-function mutations in the filaggrin gene are strongly associated with AD, clinical defects resulting from an impaired barrier can occur in the absence of any deleterious filaggrin genotypes, suggesting a role for SC lipid disruption in clinical disease [14]. Janssens et al. [14] have reported small-angle X-ray diffraction data indicative of disrupted lipid organization in patients with AD compared with subjects who have healthy skin. This variation in structure was associated with a significant reduction in ceramide content.

Much importance has been ascribed to the ceramide and cholesterol species within the SC, in part because of their higher weight contribution to the SC lipid species. In addition, pathological skin conditions, including severe xerosis, AD, ichthyoses and psoriasis, have been associated with ceramide deficiencies. However, continued research has revealed the important role of fatty acid lipids in SC barrier function and structure [8].

SC lipid structure and function

  1. Top of page
  2. SynopsisRésumé
  3. Introduction
  4. Cellular and lipid components of the SC
  5. SC lipid formation and its composition
  6. SC lipid deficiencies in skin disorders
  7. SC lipid structure and function
  8. Cleansing-induced barrier damage
  9. Strategies for lipid management in the SC
  10. Lipid-based strategies for promoting SC barrier integrity
  11. Summary
  12. Acknowledgements
  13. References

The three-dimensional organization of extracellular SC lipids has been studied extensively over the past three decades. Although consensus exists regarding the general lamellar form of the lipid structure surrounding the corneocytes, multiple hypotheses and models exist describing the details of lipid organization within the SC (see Fig. 2). X-ray studies demonstrate two characteristic spacings of 6 and 13 nanometers associated with the bilayer [8]. Models of the structural organization of SC lipids have been proposed to account for these observations. The domain mosaic model of SC lipid organization depicts the simultaneous presence of both a crystalline and a liquid crystalline lipid phase [15]. The fluid phase is thought to be discontinuous in the direction of depth; this organization allows flexibility within the lipid layer without compromising permeability barrier properties of the SC. Coexistence of both the crystalline and fluid phases is also seen in a sandwich model proposed by Bouwstra et al. [16]. The composition of the fluid phase has not yet been established. Bouwstra et al. has speculated that the fluid phase consists of cholesterol and the linoleic portion of ceramide 2 based on X-ray spacing considerations. It is possible that the fluid phase may include saturated C18 fatty acids because the combination of linoleic acid and cholesterol may be too fluid to retain SC barrier properties. Additional modeling with this specific combination of lipids may provide better insights into the fluid portion of the lipid bilayer. In contrast to the sandwich model, Norlen has proposed a gel-phase model in which SC lipids are suggested to form a single and coherent gel phase in the lower half of the SC [17].

image

Figure 2. Various models of lipid organization in human stratum corneum. Adapted with permission from Norlen, L. J Invest Dermatol. 2001;117(4):830–836 and Bouwstra, J.A., et al. Progress Lipid Res. 2003;42:1–36.

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In addition to the thickness of the bilayer, as reflected in the bilayer spacing, the packing of the lipids within a bilayer can be expected to control the overall barrier properties. Proposed forms of bilayer organization include orthorhombic, hexagonal and fluid or less rigid bilayers [8]. See Fig. 3 for different forms of bilayer arrangement within the lamellar phase. Among these three forms, orthorhombic represents the most compact packing with the highest barrier properties and the fluid form represents the least. Proportions of these may vary depending upon the relative levels of various lipids and their chain length in the bilayer [17]. SC lipid simulation studies suggest distinct roles for each lipid species within the bilayer [9]. In experiments conducted by Das et al. [9], ceramides compose a dense bilayer phase, whereas the smaller, more rigid cholesterol molecules serve to secure and condense the bilayer, thus increasing the lipid density within. In contrast, free fatty acids function to relieve the stresses induced by the dense and rigid cholesterol/ceramide bilayer [9]. It is possible that the shorter chain fatty acids (such as C18) associated with the fluid phase of the bilayer provide flexibility, whereas the longer chain fatty acids (>C20) are associated with the more rigid crystalline phase.

image

Figure 3. Stratum corneum lamellar phases and various lateral packing possibilities. Reproduced with permission from Bouwstra, J., and Gooris, G. The Open Dermatology Journal. 4, 10–13 (2010).

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Variations in the organization of lipids with depth has been reported by several investigators using a variety of measurements, including infrared (IR) spectroscopy [18], differential scanning calorimeter (DSC) and chemical composition [19]. It has been suggested that a more ordered orthorhombic structure predominates in the deeper layers of the SC, and the proportion of less ordered hexagonal or fluid phase increases in the upper layers [8]. The reason for this transformation is unclear; however, several factors may be contributory. The external factors may include the influence of sebum on upper SC layers, showering with hot water and the use of harsh, alkaline cleansers. For example, intercalation of sebaceous lipids within the SC lipids is another hypothesis that may account for the presence of medium-chain fatty acids and their ability to promote change in the rigid orthorhombic form to a less rigid form [8]. Exposure to elevated temperatures during showering or corneocyte swelling−de-swelling cycles because of cleansing with harsh products can lead to changes in the lipid structure of the upper layers. Progressive damage to skin because of external factors can eventually affect increasingly deeper layers, ultimately resulting in a breakdown of the SC barrier. In fact, in a recent in vivo study, transepidermal water loss (TEWL) has been correlated with the fraction of orthorhombic phase in the SC [20].

In addition to external factors, internal factors may influence the lipid structure of the upper layers of the SC. Bilayer lipids exist within a constrained environment among well-hydrated and swollen corneocytes during their formation in deeper SC layers, and thus may be forced into a compact orthorhombic structure. As the lipids migrate up the SC, flattening and de-swelling of the corneocytes can result in relaxation of the lipid bilayer to a less compact, hexagonal structure. Even the single gel-phase model suggests the presence of decreased order in the upper layers because of crystalline segregation and phase separation as a result of desquamation [17]. Some of these internal changes may be evolutionary in nature to accommodate external stresses and as part of the normal exfoliation process.

A more macroscopic view of SC organization in mice has emerged in which cellular clusters composed of 3–10 columns of corneocytes (described by Schatzlein et al. [21]) with tight intercalated junctions form at intra-cluster corneocyte edges through which permeability is exceedingly slow. In contrast, inter-cluster regions are suggested to be associated with less rigid and dense lipid structures and to co-localize with the superficial wrinkling visible on the skin surface [21]. Schatzlein et al. have referred to these superficial wrinkles (on a more microscopic scale than the glyph lines) as ‘canyons.’ Even though corneocyte columns such as in mice are not present in human SC, existence of ‘canyon’-like structures have been observed in human skin [22]. A discussion on canyons is beyond the scope of this publication and will be presented separately. From a materials science point of view, the presence of less rigid or fluid lipid regions in the inter-cluster region is similar to grain boundaries in organized structures, and such regions can help absorb mechanical stresses and maintain the flexibility of the SC. On the other hand, these lipid regions become more vulnerable to intercalation and extraction by cleanser surfactants. Irrespective of the specific models, the importance of SC lipids in ensuring an intact barrier with relatively low water permeability and sufficient elasticity to manage mechanical stress to the SC is well recognized by all the models.

Cleansing-induced barrier damage

  1. Top of page
  2. SynopsisRésumé
  3. Introduction
  4. Cellular and lipid components of the SC
  5. SC lipid formation and its composition
  6. SC lipid deficiencies in skin disorders
  7. SC lipid structure and function
  8. Cleansing-induced barrier damage
  9. Strategies for lipid management in the SC
  10. Lipid-based strategies for promoting SC barrier integrity
  11. Summary
  12. Acknowledgements
  13. References

Many conditions and behaviours can compromise the skin barrier, including regular body cleansing. Skin cleansing with surfactant (detergent) containing products is associated with irritation, dryness, erythema and post-wash skin tightness [23-26]. Most of the early study on cleanser-induced damage to SC focused on irritation potential of surfactants, and this has been correlated with the protein swelling potential of surfactants [25, 27]. Cleanser-induced lipid damage and its impact have received much less attention in the past [23, 28-31]. This is possibly because skin irritation linked to protein damage was the major concern in the early pre-liquid cleanser days. Imokawa et al. early on linked the role of lipid damage by surfactants to dry skin [28]. Froebe et al. concluded that lipid damage is not correlated with skin irritation and suggested that it may be linked to dry skin [32]. Attempts to correlate cleanser-induced lipid compositional changes to skin condition were rather difficult because the absolute change in the levels were low and the quantitation of such changes required detailed lipid analysis [27]. Also, the first stage of lipid damage is associated with intercalation of surfactants into the bilayer rather than extraction [33]. Continued cleansing with harsh surfactants can indeed lead to lipid removal, leading to barrier breakdown [30]. Published study in this area is reviewed here, and the implications for daily cleansing are discussed.

During cleansing, skin cells absorb water and during the post-wash drying phase the excess water evaporates off as skin equilibrates with the surrounding atmosphere [23, 29]. In the case of harsh cleansing, water uptake during the transient hyper-hydration phase is significantly higher than with mild cleansers. The increased transient water uptake is associated with binding of harsh anionic surfactants to corneocyte proteins, leading to their increased swelling [23]. Also, the subsequent evaporation results in SC that is dehydrated compared with baseline levels [34]. Such evaporation can take place at a rapid rate if the external humidity is lower. High dehydration rates may not allow normal SC relaxation processes to relieve the stress. Instead, rapid dehydration of the corneocytes can lead to their loosening and de-bonding from the surrounding lipid matrix, creating cracks and pathways for penetration of surfactants into deeper layers. The effects of hyper-hydration and rapid post-wash dehydration manifest as after-wash tightness, which is an indication of the longer term drying potential of the cleanser. In comparison, skin cleansed with water alone or ultra-mild cleansers can return to baseline hydration levels without excessive post-wash dehydration [23], causing minimal disruption to the barrier.

Cleanser surfactant molecules form self-aggregated spherical or globular nanostructures (termed micelles) in solutions above a certain concentration, referred to as the critical micelle concentration (CMC). Micelles can readily solubilize or emulsify oils and aid in their removal. Surfactants can also solubilize lipids, such as fatty acids and cholesterol. Most cleansing compositions are well above the CMC and under these conditions even a brief (<1 min) direct exposure of skin to surfactants can result in the removal of SC lipids [29]. Below the CMC, surfactants can intercalate into less rigid bilayers and weaken barrier properties [33]. In vitro studies in which SC was soaked in solutions of the anionic surfactants sodium lauryl sulfate (SLS) or linear alkyl sulfate (LAS) demonstrated that lipid removal occurs only at or above concentrations at which surfactant exists as micelles. For example, a 2% (wt/wt) solution of SLS, which is well above the CMC, was found to remove up to 7% of the total SC lipid content within 20 min of exposure to SC tissue (Fig. 4) [32]. Interestingly, the proportion of each lipid species removed did not correlate with the endogenous lipid composition of the SC.

image

Figure 4. Surfactant-induced SC lipid extraction from stratum corneum samples. Data represent percentage of total lipid content removed with surfactant treatment. Adapted from Froebe et al. Dermatologica. [32].

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Although ceramides compose approximately one-half of the SC lipid fraction, no detectable ceramide species were removed by either surfactant [32]. This result may be expected because the presence of two long hydrophobic tails in ceramides is structurally incompatible with solubilization or co-localization with micelles by typical cleanser surfactants. Because ceramides are not extracted by surfactant micelles, even under exaggerated experimental conditions, ceramides are unlikely to be extracted by cleanser surfactants during routine skin cleansing. In contrast to the observations with ceramides, 8% of free fatty acids were removed during surfactant treatment [32], indicating that fatty acids, such as stearic acid and sebaceous-derived unsaturated fatty acids, are susceptible to removal from the SC during cleanser exposure [32]. Although removal of short chain and unsaturated fatty acids of sebaceous origin is desirable as part of normal hygiene, removal of saturated stearic and longer chain fatty acids can negatively impact SC barrier properties.

Cleanser-induced removal of lipids has been studied in vivo as well. In a classic study, Imokawa et al. [28, 29] determined the kinetics of SC lipid release upon exposure of human skin to 5% sodium dodecyl sulfate (SDS). The results demonstrated lipid release of sebaceous and all SC lipids, even in 1 min, with an additional, more gradual, increase over 30 min. This result may appear to be contradictory to the in vitro results reported by Froebe et al. [32]; however, it is possible to reconcile these differences. The authors of the in vivo study noted that ‘following treatment with surfactant solution, the amounts of intercellular lipids released almost corresponded to the naturally occurring lipid composition except for free fatty acids, which are removed at a markedly higher rate considering their composition.’ In vivo one would expect exposure to surfactants to release corneocytes and associated SC lipids as part of the exfoliative process, during which release of extractable lipids because of ingress of surfactant micelles into deeper SC layers may occur. The observation that fatty acids are released at a much higher rate suggests that fatty acids are highly extractable during cleansing, and that other lipids are being released only as part of the normal exfoliation process. Our contention is that the excess fatty acid being released is from underlying layers, and that these are most likely associated with the fluid portion of the SC lipid bilayer, whereas the part that conforms to the normal SC lipid composition is associated with exfoliation. Another difference between the in vivo and in vitro study is that in the in vitro study the separation and preparation of the SC itself could have removed some of the easily removable sebaceous lipids.

Based on the above reported findings, it is reasonable to suggest that surfactant extractable fatty acid is the ‘weakest link’ in the lipid chain that composes the SC lipid matrix. Continual surfactant-induced damage to the SC with excessive fatty acid extraction may eventually result in barrier breakdown, dryness and irritation. Because maintenance of the bilayer structure of the SC requires specific ratios of ceramide to fatty acid to cholesterol, preferential removal of one of the components can lead to defects in the lipid bilayer and its subsequent destabilization. Removal of fatty acids from the fluid part of the bilayer may increase its rigidity and reduce the ability of the SC to accommodate for and permit the normal stress relaxation processes [35]. Therefore, any approach to minimizing lipid disruption should address fatty acid extractability from the SC to prevent cleansing-induced damage to deeper layers of the SC.

The functional barrier properties impacted by the intercalation of surfactants into the bilayer or surfactant-mediated lipid removal from the SC have been described by many groups. The consequences of decreased lipids include post-wash tightness (short term), dryness, cracking, perturbed desquamation, and eventually, increased TEWL and erythema. In some cases. the effect may be indirect in that alterations in the lipid layers may provide access to deeper corneocytes, which would then be susceptible to the swelling−de-swelling stresses during cleansing. Because cleanser-induced delipidation results in the removal of lipid species not covalently bound to corneocytes, significant extraction of lipids can ultimately lead to a situation in which lipids covalently bound to corneocytes from upper and lower layers can come together, resulting in abnormal inter-corneocyte adhesion and clumping of cells in the SC. Such clumping can impede normal layer-by-layer desquamation, resulting in shedding of large clumps of cells that can result in an uneven skin surface. This typically manifests as dry skin flakes in which clusters of cells separate from the underlying layers rather than the normal single cell layer desquamation. This has been demonstrated in delaminating experiments showing that inter-corneocyte adhesion is significantly higher in delipidated SC than in normal SC [36] and provides evidence for the important role of lipids in maintaining normal corneocyte adhesion and orderly exfoliation.

Strategies for lipid management in the SC

  1. Top of page
  2. SynopsisRésumé
  3. Introduction
  4. Cellular and lipid components of the SC
  5. SC lipid formation and its composition
  6. SC lipid deficiencies in skin disorders
  7. SC lipid structure and function
  8. Cleansing-induced barrier damage
  9. Strategies for lipid management in the SC
  10. Lipid-based strategies for promoting SC barrier integrity
  11. Summary
  12. Acknowledgements
  13. References

It is clear that a healthy lipid barrier is critical to a healthy SC. When a barrier is acutely compromised, skin's natural biological processes are activated in response. Endogenous lipid synthesis repair mechanisms are initiated rapidly in hairless mice following mechanically (tape stripping) or chemically (solvent or detergent) induced barrier disruption [3]. Within minutes, lamellar body secretion increases markedly and continues until barrier function is fully restored [3]. All of the major SC lipid species increase in expression after barrier challenge; however, the delay between onset of challenge and onset of lipid repair differs. Synthesis of both fatty acid and cholesterol is rapidly up-regulated post-challenge [3, 37]. Unlike the immediate response to barrier damage that occurs with fatty acid and cholesterol regeneration, the synthesis of the ceramide precursors, sphingolipids, does not increase until nearly 6 h post-challenge [3]. These varied responses suggest an important role for fatty acids and cholesterol in the early phases of barrier repair following acute insult, and the requirement for ceramides may present during a later phase of recovery.

Lipid-based strategies for promoting SC barrier integrity

  1. Top of page
  2. SynopsisRésumé
  3. Introduction
  4. Cellular and lipid components of the SC
  5. SC lipid formation and its composition
  6. SC lipid deficiencies in skin disorders
  7. SC lipid structure and function
  8. Cleansing-induced barrier damage
  9. Strategies for lipid management in the SC
  10. Lipid-based strategies for promoting SC barrier integrity
  11. Summary
  12. Acknowledgements
  13. References

Topical moisturizers are generally designed to indirectly increase skin hydration by minimizing the evaporation of water from the SC [38, 39]. Occlusive moisturizers, such as petrolatum, are effective for reducing water evaporation from the SC and are present in many commercially available moisturizers. Emollient oils are commonly used to lubricate the SC and reduce cracking in dry skin [40, 41]. Recent advances in moisturizer technology have included the topical application of lipid species naturally found within the SC. Research conducted by several groups has demonstrated significant barrier benefits following application of mixtures containing ceramides, cholesterol and fatty acids [42-44]. Notably, the data suggest that a physiologically relevant proportion of each component is necessary to promote barrier restoration [38-40]. Although moisturizer strategies promoting lipid-focused hydration of the SC barrier are an important aspect of basic skin care, our study has focused on the role of minimizing damage to lipids proactively during cleansing, replenishing components that are likely to be lost and ensuring conditions that will allow skin's natural biology to build a healthy barrier.

Historically, formulations of skin cleansers included alkyl carboxylate surfactants, commonly referred to as soap [23, 42, 45, 46]. Significant understanding of the deleterious effects of soap on skin has demonstrated the need for milder cleansing alternatives.

The advent of synthetic detergent (syndet) bars in the late 1950s introduced a milder surfactant, sodium alkyl isethionate, with a neutral product formulation [47]; a significant improvement over its harsh, basic predecessors. Dove® syndet cleansing bars, and the more recently introduced Dove® liquid body cleansers, utilize a unique and proprietary combination of a mild surfactant system with skin natural moisturizing agents [48].

In general, use of a liquid cleanser lacking moisturizing ingredients is associated with delipidation of the fatty acids and cholesterol in the SC, even after a single wash [23]. Approaches employed in current formulations of moisturizing body cleansers include the use of moisturizing agents that may promote increased hydration by filling in superficial cracks in skin and providing occlusion to promote water retention in the SC and by increasing absorption of water from the external environment. However, most products are not designed to prevent lipid removal or replenish the specific lipid components of the SC lost during cleansing [48].

We have previously published on the benefits of a novel body wash designed to minimize surfactant-induced protein and lipid damage [48]. Briefly, the directly esterified fatty isethionate (DEFI) surfactant system in the body wash was pre-saturated with stearic acid to minimize lipid extraction from the SC and enhance the mildness properties of the surfactant [48]. This surfactant−lipid combination system demonstrated significant reductions in both TEWL and visual dryness compared with the surfactant system without lipids (Fig. 5).

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Figure 5. The effect of fatty acids in a DEFI-based cleanser on TEWL and clinical dryness. TEWL was recorded as grams of water lost per metre square of skin per hour. Visual assessment of dryness was rated on a scale of 0–6, where 0 = none and 6 = severe. Data represent changes from baseline assessments. N = 15 subjects. Asterisk indicates significant difference (< 0.05) from DEFI surfactant. Reprinted with permission from Cosmet Dermatol. 2009;22:307–316. ©2009, Quadrant HealthCom Inc. [48]

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In contrast to occlusive or emollient ingredients that impact the SC primarily at the surface, the stearic acid within the DEFI surfactant system is physiologically relevant at the molecular level and is incorporated into the SC. In Mukherjee et al. [7], we reported on the physiological incorporation of deuterated stearic acid molecules delivered via a lipid-rich body wash. The applied stearic acid penetrated into each of the consecutive SC layers tested (10 layers) and replaced a quantity of fatty acid similar to that removed during a typical wash [49] (Fig. 6A). We also demonstrated that the amount of stearic acid deposited on skin is higher in the presence of triglyceride oils than with petrolatum (Fig. 6B). This may be because of triglyceride oil acting as a carrier for fatty acids, aiding both deposition and penetration.

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Figure 6. Tape stripping analysis of deuterated stearic acid deposition into the SC following 5 days of sample product use. Stearic acid deposition within the top 10 tape strips (A) and total amount of stearic acid deposited within the SC (B). Blue data indicate stearic acid−containing body wash supplemented with soybean oil (formulation #1); grey data indicate stearic acid−containing body wash supplemented with petrolatum (formulation #2). N = 20 subjects. Mukherjee S, Edmunds M, Lei X, Ottaviani MF, Ananthapadmanabhan KP, Turro NJ. J Cosmet Dermatol. 2010;9(3):2022–10. © 2010 Wiley Reproduced with permission of Wiley. [49].

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Although the role of stearic acid in cleansers is to minimize lipid damage and replenish fatty acids in the SC, emollient oils and occlusives provide an immediate visual benefit and a reduction in water loss. The latter is relevant when the SC is dry, whereas the role of fatty acid in preventing damage and protecting the barrier is relevant for both normal and dry skin. Body wash technologies with ceramides and emollient oils have begun to appear in the marketplace. In most cases, the ceramides used in these products are pseudoceramides rather than actual physiological SC ceramides. Thus, the ceramides in such products cannot replenish actual SC ceramides. Because ceramides are not likely to be extracted by cleanser surfactants, the question of replenishing ceramides does not present itself in the context of normal skin cleansing. Use of ceramides along with other emollients will indeed provide moisturization as expected from a lipid moisturizer, but not necessarily a lipid replenishment mechanism, as outlined here for stearic acid.

Conti et al. [50] have reported that use of certain triglyceride oils can enhance ceramide synthesis within the SC. This approach of providing lipid precursors for the SC to utilize in lipid synthesis and ensuring that the enzymes involved in lipid synthesis (e.g., beta glucocerebrosidase) are not affected by surfactants is an effective way to build a healthy barrier. In this regard, use of ultra-mild surfactants with fatty acids and triglycerides in a cleanser can be expected to lead to a healthier SC, as demonstrated by the previously reported clinical benefit of such a cleanser formulated in combination with fatty acids and triglycerides [49]. Although all forms of surfactant-based cleansing result in damage to the SC, a surfactant system in which skin identical fatty acids are added to a mild cleanser base can reduce the clinical consequences of such damage.

Summary

  1. Top of page
  2. SynopsisRésumé
  3. Introduction
  4. Cellular and lipid components of the SC
  5. SC lipid formation and its composition
  6. SC lipid deficiencies in skin disorders
  7. SC lipid structure and function
  8. Cleansing-induced barrier damage
  9. Strategies for lipid management in the SC
  10. Lipid-based strategies for promoting SC barrier integrity
  11. Summary
  12. Acknowledgements
  13. References

In this review, we focused on the role of lipids and lipid management from a cleansing perspective. The disproportionately high degree of fatty acid extraction with surfactant use underscores the importance of addressing this lipid species during body cleansing. The contribution of fatty acids to bilayer lipids in the SC and to its strength and flexibility in withstanding mechanical stresses further highlights the need to preserve fatty acids while promoting barrier integrity. Utilization of mild and moisturizing cleansing technologies that simultaneously enhance lipid protection and replenishment is an important strategy in maintaining healthy skin and promoting a healthier barrier in compromised or diseased SC.

References

  1. Top of page
  2. SynopsisRésumé
  3. Introduction
  4. Cellular and lipid components of the SC
  5. SC lipid formation and its composition
  6. SC lipid deficiencies in skin disorders
  7. SC lipid structure and function
  8. Cleansing-induced barrier damage
  9. Strategies for lipid management in the SC
  10. Lipid-based strategies for promoting SC barrier integrity
  11. Summary
  12. Acknowledgements
  13. References
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