Cumulative (Longer-Term) Effects of Repeated Exposure to Surfactants in .NET

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Cumulative (Longer-Term) Effects of Repeated Exposure to Surfactants
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Continued daily use of cleansers that cause short-term damage can lead to skin dryness, scaling, flaking, erythema, and pruritus21 While detailed molecular mechanisms involved in these effects have not been fully elucidated, based on current understanding, several possible mechanisms can be hypothesized as detailed below
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Dryness, Scaling, and Flaking
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Skin dryness, or xerosis, is more than just a lack of water in the SC (see 11) It is actually a disruption in the biologic processes underlying healthy normal skin, which affects clinical as well as patient/consumer perception of skin condition Consumer perception of dryness has both a visible and a tactile component Visual effects
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% Zein protein dissolution in 5% surfactant solution
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Erythema and Pruritus
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Erythema and pruritus are essentially inflammatory responses of the skin when irritants, such as surfactants, penetrate into deeper layers of the SC In the cleansing context, this is usually because of a breakdown of the barrier for reasons indicated above, leading to penetration of irritant materials Note, however, that it may not be necessary for the surfactant to penetrate into dermal layers to elicit a response Communication via production of cytokines in the SC can also elicit a response from the dermis21 Factors that enhance the penetration of surfactants can be expected to increase surfactant-induced irritation Thus, a swollen SC will allow increased penetration of the surfactant into deeper layers The ability of a surfactant to swell the SC is an indication of its ability to enhance its own penetration into deeper layers and disrupt the cells in the living layer This may be the scientific basis for the established correlation between the ability of surfactants to swell the SC and its irritation potential If the swelling occurs by other mechanisms such as an increase in the protein negative charge because of high solution pH,25 penetration of surfactants can also be expected to be enhanced under these conditions Thus, the direct effect of pH 10 by itself on the SC could contribute to increased surfactant irritation Changes in lipid layers at pH 10 may also impact irritation in that their increased rigidity may render them more vulnerable to cracking and debonding from the corneocytes thereby permitting penetration of irritants
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12 Active in soap bars 10 Active in liquids 8 Active in syndet bars 6
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FIGURE 31-6 Protein damage potential of a number of surfactants determined using the zein dissolution test The higher the zein dissolution, the higher is the damage potential of the surfactant (Reproduced from Ananthapadmanabhan KP, Subramanyan K, Nole G Moisturizing cleansers In: Loden M, Maibach H, eds Dry Skin and Moisturizers, Chemistry & Function 2nd ed Boca Raton, FL: CRC Press; 2006:405-428) swell the SC,15,24 model proteins such as collagen26 and keratin,27 denature a globular protein such as BSA,28 or dissolve a water-insoluble hydrophobic protein such as zein,29, 30 the greater is its tendency to irritate human skin Results of zein solubilization by several surfactants are provided in Fig 31-6 As can be seen, the proclivity of surfactants to interact with proteins follows the order: anionic amphoteric nonionic This is consistent with the published results revealing the protein-damaging predispositions of various classes of surfactants Figure 31-6 also shows the syndet bar active ingredient sodium cocoyl isethionate to have significantly less interaction with proteins than soap This can be attributed to its larger head group area and lower micellar charge density as compared to sodium soaps Similarly, the commonly used surfactant system for liquid cleansers, a combination of sodium lauryl ether sulfate (SLES) and cocoamido propyl betaine (CAPB), is significantly milder than soap Table 31-2 displays a list of commonly used cleanser surfactants classified as relatively harsh or mild While these empirical correlations are useful as guidelines for formulation work, quantitative associations between surfactant properties and their protein denaturation propensities are most useful as a predictive ruler Based on the hypothesis that protein denaturation is essentially due to massive cooperative binding of surfactants on the protein backbone and the resultant increase in the charge of the protein, surfactant micellar charge was correlated with the zein dissolution tendencies of various surfactants Protein denaturation has been shown to scale linearly with the charge density of surfactant micelles31 This insight has allowed formulators to develop novel strategies to predict and increase the mildness of cleanser bases In general, micelle charge density can be lowered by using surfactants of larger head groups, zwitterionic or nonionic head groups, and a synergistic combination of surfactants that allow strong attractive interactions among head groups leading to a reduction in the overall charge density of the micelle
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