No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Exfoliation for sensitive skin with neutralized salicylic acid?
Abstract
Citation: IFSCC Magazine, 11 (2008) (2) 115–119
Abstract: Hydroxy acids enjoy tremendous interest in cosmetology thanks to their skin anti-ageing and water barrier enhancing activities. One of their actions is to promote the natural stratum corneum (stratum corneum) desquamatory process. However, their use is limited due to an inherent pH-related irritancy potential which is even more exacerbated on sensitive skin. Clearly there is an opportunity for improvement. In this research we evaluated in humans the efficacy of salicylic acid, and its salts, as a corneodesmolytic agent using the dihydroxyacetone method and measuring the reduction in skin staining with treatment over time using a chromameter. Salicylic acid at 2% in a preparation of pH 3.12 significantly increased exfoliation by 10.9% compared with placebo (P < 0.05), confirming its desquamatory enhancing properties. Then the effect of vehicle cream pH on salicylic acid activity was studied. Salicylic acid at close to neutral pH (mostly in its neutralized form as salicylate, pH 6.50) exerted a corneodesmolytic activity as good as that of salicylic acid in an acidic vehicle (pH 3.12) after only two days of application. Furthermore, the performance of glycolic acid and salicylic acid salts as exfoliants were compared at pH 6.50. When these two hydroxyl acids were formulated at the same molar level in a cosmetic base (14.47mmol L-1), the salicylic acid preparation gave an 8.2% increase in stratum corneum desquamation compared with the glycolic acid preparation (P < 0.05). The corneodesmolytic effects were confirmed using a tape-stripping assay combined with a quantitative protein assay. Neutralized salicylic acid was found to enhance the removal of stratum corneum proteins significantly more than the vehicle after 25 sequential tape strippings (14%; P < 0.05). Finally, salicylic acid had no significant influence on skin water barrier properties after 22 days of treatment. In the second phase of this research we assessed the suitability of neutralized salicylic acid as an ingredient for sensitive skin. A stinging test was performed according to the Frosch & Kligman method to evaluate the influence of the formulation base-pH on stinging potential. Salicylic acid formulated at pH 6.50 induced no stinging sensation (score 0) in contrast to salicylic acid at pH 3.12 (score 19; P < 0.05). In addition, a clinical study was conducted to assess the erythema induced on volunteers’ cheeks after a single application of a neutralized salicylic acid (1%) formulation compared with placebo. Visual redness was assessed by a dermatologist and then measured with a Mexameter. No significant differences were observed. Moreover, half of the panel had sensitive skin and no correlation could be established between redness and/or abnormal sensation and sensitive skin. In conclusion, neutralized salicylic acid at a 1% concentration is a suitable exfoliant agent for subjects with sensitive skin.
Keywords: exfoliation, hydroxy acids, Salicylic acid, stratum corneum
Paper presented at the IFSCC Conference 2007, Amsterdam, The Netherlands.
... PT (Penta erythritol tetra acrylate) is a tetra-functional acrylate monomer widely used as crosslinker in polymerization. In previous studies, PT has been used as crosslinker for polyethylene oxide (PEO) via UV radiation [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] and for HA via exposure to high temperature (80 • C) in the oven [12]. Such crosslinked hydrogel films can be suitable for the delivery of drugs and cosmetic active ingredients by transdermal and topical (cosmetic) formulations, respectively, via application of the hydrogel film on the intact skin surface. ...
... Also, SA is keratolytic, which allows it to be utilized in wart healing [24] and as anti-comedogenic in acne. The carboxylic group in the SA structure allows H-bonding interactions with other ingredients and with structural polymers in pharmaceutical and cosmetic formulations, therefore enabling a high loading capacity in the vehicle [25]. The low molecular weight of SA (138 Dalton) enables its molecular diffusion via the stratum corneum for either a topical (cosmetic) or transdermal (pharmaceutical) effect. ...
... where Qv 5 3 is the volumetric swelling ratio, v is the specific volume of the dry polymer (v = 0.575 cm 3 /g for HA), v 1 is the molar volume of the solvent (18 cm 3 /mol for water), and x is the Flory polymer solvent interaction parameter (for HA). The x value was estimated to be 0.473 based on several assumptions [13,25]. Qv was determined as Q m , which is the degree of mass swelling, according to Equation (5). ...
Novel crosslinked hyaluronic acid (HA) hydrogel films were previously invented by reacting the HA polymer with the PT (Pentaerythritol Tetra-acrylate) crosslinker over basic pH conditions in the oven. HA is considered a natural polymer present in cosmetic as well as pharmaceutical formulations. This current study aimed to highlight the effect of loading method (post-loading and in situ) of selected actives (salicylic acid and niacinamide B3) in the hydrogel films and then study their release kinetics. Differential scanning colometry (DSC) and Fourier transform infrared spectroscopy (FTIR) analysis evidenced the loading of the actives and full release from the HA hydrogel films, while the scanning electron microscopy (SEM) demonstrated the morphological changes to the films during the study by comparing the average molecular weight between crosslinks (M¯c), gel fraction, crosslinking density (Ve) and mesh size (ξ) of the films. The loading percentage of the SA and B3 showed high percentage loading of actives via both loading methods. In conclusion, the (95–100%) release of the actives achieved from the HA hydrogel films within 10 min revealed that the films are an efficient immediate release system of actives.
... We were especially interested in this approach and we also demonstrated that sodium salicylate (SS) displayed equivalent corneodesmolytic activity, as measured using a SC turnover assay having stained the SC with dihydroxyacetone and measuring its removal using a chromameter, compared to SA at an acidic pH. 29 Furthermore, SS displayed a greater efficacy in comparison with an equimolar level of glycolic acid formulated at pH 6.5. 29 Importantly, this formulation was not only capable of reducing skin irritation but also possessed no somatosensory irritation problems in subjects with sensitive skin. ...
... 29 Furthermore, SS displayed a greater efficacy in comparison with an equimolar level of glycolic acid formulated at pH 6.5. 29 Importantly, this formulation was not only capable of reducing skin irritation but also possessed no somatosensory irritation problems in subjects with sensitive skin. Nevertheless, the choice of an optimum emollient system was critical for the latter benefit. ...
... In this respect, our aim was to develop a nonstinging SA formulation that has anti-aging benefits. In previous studies, SS has been proven to induce SC exfoliation 28,29 and we know that exfoliation by various means has been shown to provide anti-aging skin effects. 13,14 Here, we provide evidence for the anti-aging effects of SS at the clinical and histologic level. ...
Anti-aging effects of high concentrations of salicylic acid (SA) peels are commonly known. Like all acids, SA can produce somatosensory and visible irritation to the skin and as such may be unsuitable for subjects with sensitive skin.
To provide evidence that sodium salicylate (SS) obtained from neutralization of 1% SA by sodium hydroxide can deliver significant anti-aging benefits.
The effects of SS were examined using three approaches: (1) evaluating its effects on stimulating the synthesis of fibrillin and collagen-1 in vivo; (2) examining its efficacy by using Fast Optical in vivo Topometry (FOITS) in a double-blind, placebo-controlled clinical study; (3) determining its effects on both expert and naïve grader assessement of wrinkles in a double-blind, placebo-controlled study.
In the first study SS produced significant increases of the fibrillin and collagen-1 anti-aging biomarkers compared with the untreated skin control. A commercially available retinol cream delivered similar effects to SS. In the second study using FOITS we showed that the SS formulation significantly reduced wrinkle depth (Rz) and skin roughness (Ra) after 4 and 8 weeks of daily application vs. placebo (Rz: -8.2 ± 1.40% and -11.4 ± 1.07%; Ra: -7.8 ± 1.33% and -11.9 ± 0.61%; P < 0.01). In the third study reductions in wrinkle depth were observed by expert assessment at both 4 and 8 weeks for the SS-containing formulation compared to its placebo (P < 0.05). Equally, non-expert graders recorded the SS formulation superior to its placebo.
Although the mechanism of action is not completely understood, we believe the benefits of SS are derived from its intrinsic stratum corneum exfoliation effects. All three studies demonstrate the significant anti-aging effects of SS that are especially suitable for subjects with sensitive skin.
... enticing women to extend their routine 3 and the promotion of multi-step regimens by celebrities and influencers. 3,4 While countless vehicle-controlled studies have demonstrated about the benefit of actives over a vehicle alone and/or vs gold standard ingredients, [5][6][7] clinical evidence about the benefits of a skin care routine remains scarce, despite the claimed benefits of using products as part of a regimen. Reported efficacy of regimens is available in the dermatological field, to address skin conditions such as acne, 8,9 atopic dermatitis, or rosacea. ...
Background:
The use of a skin care routine is commonly promoted by the cosmetic industry, yet there is a lack of clinical evidence to support this practice over the use of a single skin care product.
Aims:
In the present study, we aimed at showing the clinical benefits of using a comprehensive skin care routine vs a simple one.
Methods:
Skin micro-/macro-topographic, skin color, and superficial/deep hydration were collected at baseline and after 4 weeks of use, on forty-nine women randomly allocated to two groups. The first one followed the use of an advanced routine (AR: Cleanser/Toner/Eye cream/Serum/Day & Night cream), while the other group was instructed to use a simple routine (SR: Cleanser & Day cream).
Results:
Hemoglobin heterogeneity was found to be significantly reduced only in the SR group. However, the AR outperformed the SR when it comes to improving superficial hydration, deep hydration, skin roughness, mean pore area, melanin heterogeneity, and crow's feet wrinkle depth. A significant increase in skin brightness from baseline was only recorded when using the AR while both routines significantly improved the nasolabial wrinkles.
Conclusion:
These findings advocate for using a relevant daily routine as it demonstrates the visible skin benefits over a short period, while driving the creation of habits for the prevention of aging signs.
... Salicylic acid formulated at pH 6.50 induced relatively no stinging compare to a formulation at pH 3.12. [68] The general approach is to use these agents in patients with darker skin to simultaneously treat active lesions and to correct postinflammatory changes. [69,70] In addition, acne scars have been found to improve using these agents. ...
Conventional acne treatment presents several challenges such as intolerable side effects and antibiotic resistance. Dermocosmetic products may be used to reduce these unwanted effects. Dermocosmetics include skin cleansers, topical sebum-controllers, skin antimicrobial/anti-inflammatory agents, moisturizers, sunscreens, and camouflage products. Appropriate use of these products may help augment the benefit of acne treatment, minimize side effects, and reduce the need for topical antibiotics. In Asia, there is currently limited scientific data on the application and recommendations for dermocosmetic use in acne vulgaris (AV). This article reviews the evidence on dermocosmetics for AV and provides practice recommendations as discussed during the 4(th) Asia-Pacific Acne Leaders' Summit held in Bangkok, Thailand, on 7 and 8 February 2015. Through a premeeting survey, a series of plenary lectures, a stepwise program of discussion sessions, and Medline article review, the Expert Panel set forth relevant recommendations on the role of dermocosmetics as adjunct for treating AV in Asian patients.
Objective
The treatment of acne presents a major clinical and dermatological challenge. Investigating the nanomechanical properties of precursor lesions as microcomedones using atomic force microscopy (AFM) may prove beneficial in understanding their softening, dissolution, and prevention.
Methods
Therefore, to support this exploration, sodium salicylate (NaSal), a common ingredient employed in skin care products, is applied ex vivo to micocomedones and their nanomechanical properties are assessed using AFM. Although the exact biochemical mechanism of NaSal on microcomedones is not fully understood at present, it appears to exhibit a significant exfoliation effect on the skin via corneodesmosome dissolution.
Results
Herein, our findings demonstrate that when microcomedones are treated with 2% NaSal, samples appeared significantly more compliant (“softer”) ((1.3 ± 0.62) MPa) when compared to their pre-treated measurements ((7.2 ± 3.6) MPa; P = 0.03826). Furthermore, elastic modulus maps showed that after 2% NaSal treatment, areas in the microcomedone appeared softer and swollen in some, but not in all areas, further proving the valuable impact of 2% NaSal solution in altering the biomechanical properties and morphologies in microcomedones.
Conclusion
Our results are the first of their kind to provide qualitative and quantitative mechanobiological evidence that 2% NaSal decreases the elastic modulus of microcomedones. Therefore, this study provides evidence that NaSal can be beneficial as an active ingredient in topical treatments aimed at targeting microcomedones.
There is a growing body of evidence showing the benefit of some common cosmeceutical agents in the various pathogenic stages of acne. Sarah Boxley explains why an understanding of the roles of these products, the evidence to support their use, and their potential side effects, should enable practitioners to effectively and appropriately advise patients on their benefits and limitations
There is a growing body of evidence showing the benefit of some common cosmeceutical agents in the various pathogenic stages of acne. Sarah Boxley explains why an understanding of the roles of these products, the evidence to support their use, and their potential side effects, should enable practitioners to effectively and appropriately advise patients on their benefits and limitations
Hydroxy acid has been used to enhance anti-aging and skin moisturization by peeling effect on the skin stratum corneum, and thus it has been widely used in topical products and cosmetic products. Among them, the effect that appears most effectively in a short period of time has been reported to be effected by the pH of the cosmetic formulations. However, there are many difficulties in use due to irritation caused by pH and concerns about side effects. The purpose of this study was to evaluate the effect of applying cosmetics with (1) varying concentrations, (2) types and (3) pH of hydroxy acid on human skin. 22 healthy adults were stained with DHA (dihydroxyacetone) and DC (dansyl chloride) on the forearm, and the skin exfoliation effect was measured after application of the test products. (1) The application of GA (glycolic acid) increased the desquamation by concentration dependent. (2) the test product prepared with neutral pH showed no exfoliation effect. In contrast, SA (salicylic acid) showed a statistically significant exfoliation effect at both acidic pH and neutral pH. (3) The neutral pH SA showed excellent exfoliation effect on bot DHA and DC stained stratum corneum. These results suggest that it is possible to manufacture safe cosmetics without damaging the skin barrier, providing an opportunity to use cosmetics that are expected to exfoliate to people, whose skin is sensitive to pH.
Tape-stripping of the skin is a useful method for removing the stratum corneum and obtaining more information about the function of this skill layer as the main barrier for skin penetration. The amount of stratum corneum removed is of relevance in establishing the concentration profile of chemicals within the stratum corneum after topical application. Weighing is the preferred method for measuring the amount stripped, but because it is often subject to artifacts, alternative methods are sought. We present a simple, colorimetric method for determining the amount stratum corneum removed by sequential adhesive-tape-stripping of human skin in vivo. The method is based on quantification of the sodium hydroxide soluble protein fraction using a commercially available protein assay similar to the Lowry assay. The method is shown to be an accurate and reproducible alternative to weighing, also demonstrating uniform removal of stratum corneum layers following the very initial strips.
Hydrophilic ointment formulations containing salicylic acid were prepared at different pH levels by inclusion of phosphate buffers. Percutaneous salicylic acid absorption was studied by measuring salicylate blood levels in rabbits at 1.5-hr. intervals from 1.5 to 7.5 hr. after ointment application. The effect of 15% dimethyl sulfoxide in the various formulations was also determined. Formulations without dimethyl sulfoxide produced maximal blood concentrations at the highest pH level (10.78) and higher concentrations at the lowest pH (2.97) than at the intermediate ones (4.48, 6.80, 9.23). Proportionally higher concentration of undissociated species appeared to account for the increased absorption observed at the most acidic pH, while increased dissolution was probably responsible for the greater blood levels recorded at the most alkaline pH. Dimethyl sulfoxide produced a more rapid rate of salicylate absorption as well as greater peak blood levels at each pH. However, its influence on rate of absorption and on peak blood levels was less pronounced at the highest pH levels. This finding seems to indicate that the positive effect of dimethyl sulfoxide on percutaneous salicylate absorption is due in part to its ability to enhance the dissolution of salicylic acid.
Synopsis The evaluation of sun-product efficacy, with laboratory solar simulators or in actual sun, implicates clinical and subjective assessment of the various skin responses in terms of wavelengths constitutive of solar light. These photobiological responses vary according to skin types and particularly to basic skin melanic content, i.e. with skin colour. Now, the instrumental measurement of live skin colour has become easier to perform, fast and reliable. Based on the standard CIE-L*a*b* colour system and correlated with the human eye, this technique was used to define the skin colour domain of the caucasian population, to propose a skin colour classification, and then to objectively follow, over a three week period, the dynamics and kinetics of tanning induced by UVB, UVA and UVB +/- A multi-exposures on the three skin categories. The specific directions in the three-dimensional L*a*b* colour space of the tanning components, i.e. erythema, immediate pigmentation and constitutional melanization, as well as the resulting tanning pathways, were analysed and defined in the three-dimensional colour space, using a vectorial method. The UVB, UVA and UVB +/- A tannings were differentiated by their intensity, their hue and especially their lasting capacity: UVA tanning clearly appeared more lasting than UVB. In addition, the UVA*UVB interaction on tanning intensity was not found to be significant. With the skin colour classification and the tanning models, this comprehensive study supplies a basic tool for the colorimetric interpretation of the skin phenomena involved, provided that this interpretation is always considered in the three dimensions of the colour space. It also suggests some useful practical applications for sun product formulation and evaluation.
The hazards of the dansyl chloride test are not negligible. We introduce the dihydroxyacetone test as a safe substitute. Several advantages are highlighted including easy and reproducible measurements of the modifications in skin color by chromometry in the L* a* b* (luminance, hue, chroma) mode. The color variations in time as well as the fade-out of DHA-induced pigmentation by some cleansing skin care products are revealed 'in vivo' as well as 'ex vivo' on D-Squame collections of stratum corneum.
The purpose of the present study was to compare Franz cells (FC) and microdialysis (MD) for monitoring the skin absorption of salicylic acid (SA). The influence of pH on SA flux was also assessed by these two techniques. Excised abdominal human skin was used in the experiments. SA was dissolved in phosphate buffer solutions of pH 2, 5 and 7 (2 mg/ml). SA concentrations in the receptor FC solutions and in MD samples were assessed by high performance liquid chromatography (HPLC). The results demonstrate that the flux of SA decreased with increased pH. The profiles permeation determined by Franz cells and microdialysis were similar. However, whatever the pH, the SA flux was higher with microdialysis than with Franz cells. The results showed that SA percutaneous permeation conformed to the pH partition hypothesis. The flux of SA was different when it was determined by the two techniques. The collect of SA, by these two techniques is different. The results of the two techniques are compared and discussed.
Keratolytic efficacy of topical preparations containing salicylic acid was studied in humans utilizing adhesive tape stripping and quantifying SC removal by protein analysis. In combination with tape stripping, squamometry was used to evaluate the influence of salicylic acid on skin surface scaliness and desquamation. Furthermore, skin barrier perturbation and skin irritancy was recorded and related to the dermatopharmacological effect of the preparations. In contrast to squamometry, tape stripping combined with protein analysis was sensitive in detecting keratolytic effect of salicylic acid within hours of application. Importantly, whereas the pH of the preparations only minimally influenced efficacy, local dermatotoxicity was significantly increased at acidic pH. This indicates that the quest to increase the amount of free, non-dissociated SA is, in fact, counterproductive as the more acidic preparations resulted in skin irritation and barrier disruption.
Examination of stratum corneum (SC) content with tape stripping and a colorimetric method is increasingly used. We examined the possible use of microplates in tandem with a colorimetric method to examine SC removed with tape stripping. As a corollary to this examination, the homogeneity of tape strips was examined.
The commonly used Lowry assay was adapted for 96-well plates. Tapes were divided into four regions and sample disks of 5 mm diameter were taken from each and analyzed for SC mass using the adapted Lowry assay.
Homogeneity of SC removal over different areas across a tape strip is limited.
Quantification of SC by means of a 96-well microplate-based colorimetric method is feasible and shortens the time of analysis. However, when using D-Squame tape disks, SC removal on a limited area of the tape is not predictive for SC removal on the entire tape as removal is inhomogenous. Therefore, SC protein extraction should be performed on a large enough area, eventually on the entire tape when quantifying SC mass removed by tape stripping.
Retinoic acid (RA) and benzoyl peroxide (BP) were studied, comparing their keratolytic efficacy and water barrier disruption to that of salicylic acid (SA), a well-established keratolytic, under similar conditions.
Six volunteers were included in this blinded study. Eleven randomized test sites were marked on the volar forearms, containing sites for untreated skin at time zero, unoccluded, occlusion, and vehicle controls for 3 and 6 h, and each of BP, RA, and SA solutions for 3 and 6 h. At each time point, occlusion at 5 of the test sites was removed, and chromameter measurements were performed over 30 min. Each site then underwent 25 stratum corneum (SC) tape strippings. At 1, 5, and 30 min after the last stripping at each site, TEWL measurements were performed. Quantitative protein analysis of the SC from the tapes was then performed.
after 3 h, bp was significantly more effective in disrupting sc cohesion than sa and ra, indicating bp is a moderate keratolytic agent in addition to its antimicrobial properties. After 6 h, all three agents were similarly effective in keratolysis. Barrier disruption, as measured by TEWL, paralleled depth of SC removal. SA tended to exhibit the greatest keratolytic efficacy superficially, hence its clinical effectiveness in superficial conditions such as comedonal acne, whereas BP was more effective at deeper levels, complimenting its antimicrobial effects and enabling it to treat deeper, more inflammatory lesions. None of the agents significantly affected skin erythema. These techniques provide a robust and rapid assay for in vivo keratolytic demonstration.
Tape stripping is an established procedure in stratum corneum (SC) physiology research. Adhesive films are pressed to the surface of the skin and then removed. The superficial layers of the SC adhere to the film and are accessible for further investigations. Although this method is widely used, only scant information about standardization is known. Various protocols are used but are difficult to compare.
The aim of the present study was to investigate the effects of the type of tape, pressure, time, anatomical site and type of applied pressure.
Twelve healthy volunteers (age range 20-31 years) were entered in a randomized, controlled study with sequential tape stripping at the volar forearm, upper arm, cheek and back. Different methods (roller, stamp, thumb, stretched skin), total duration of applied pressure (2 s, 10 s), degrees of pressure (2 N stamp, 7 N stamp) and different tapes (D-Squame, Corneofix, Blenderm) were investigated and the impact on barrier function assessed by transepidermal water loss measurements. Furthermore, measurements of SC hydration, skin colour and skin surface pH were performed. Spectroscopic measurements and a Bradford protein assay to determine the mass of removed SC were carried out in parallel.
The degree of barrier disruption, irritation and SC cohesion is influenced by the character of adhesive tapes, total duration of applied pressure (2 s, 10 s; 2 N, 7 N), the kind of method for pressure application (roller, stamp, thumb, stretched skin), anatomical site and condition before stripping (occlusion vs. nonocclusion). The spectroscopic assessment and Bradford protein assay determination showed a significant correlation (P < 0.0001; r = 0.7041).
The present study showed significant differences between different factors on controlled barrier disruption. The results indicate the importance of defining these factors when a study is initiated and when results of different studies should be compared. Based on our data we propose using a 2 N stamp for a duration of 2 s on 15 sequential D-Squame tape strips on the volar forearm and then discarding the first and second strips. This approach allows the performance of a standardized study with a reasonable amount of resources.
Sensitive skin is a condition of subjective cutaneous hyperreactivity to environmental factors. Subjects experiencing this condition report exaggerated reactions when their skin is in contact with cosmetics, soaps and sunscreens, and they often report worsening after exposure to dry and cold climate. Although no sign of irritation is commonly detected, itching, burning, stinging and a tight sensation are constantly present. Generally substances that are not commonly considered irritants are involved in this abnormal response. They include many ingredients of cosmetics such as: dimethyl sulfoxide, benzoyl peroxide preparations, salicylic acid, propylene glycol, amyldimethylaminobenzoic acid and 2-ethoxyethyl methoxycinnamate. Sensitive skin and subjective irritation are widespread but still far from being completely defined and understood. The aim of this paper is to summarize the relevant literature in order to elucidate the underlying mechanisms of sensitive skin and the best testing methodologies for investigation of sensitive skin.