Stratum Corneum Surface Research Articles

What defines dry skin? Correlating a range of skin hydration parameters with InVivo Confocal Raman Spectroscopy.

While there are a wide range of approaches for the assessment of skin hydration, it is not always clear how data from them relate to one another or to the skin itself. With the development of invivo Confocal Raman Spectroscopy (ICRS), it has become possible to measure water concentration as a function of protein/depth within the stratum corneum (SC). This article reports a comparison between electrical skin hydration measures/visual/optical grading and water concentration profiles measured using ICRS, to better understand the relationship between these approaches. SC hydration of lower-leg skin with varying degrees of dryness was assessed using visual grading (live and from digital images), Corneometer®, Visioscan and ICRS. In addition, a custom fingerprint sensor was used to image surface capacitance (as a surrogate of SC hydration), and SC barrier function was assessed using evaporimetry (to measure trans-epidermal water loss; TEWL). Significant correlations were observed between a number of different skin grading/measurement approaches and ICRS data. ICRS hydration profiles also revealed a region near the SC surface with a relatively flat water profile in dry skin subjects. The advent of quantitative invivo analytical techniques such as ICRS, which can be used in a clinical setting, has enabled greater insight into more conventional approaches for assessing skin dryness. While traditional skin grading and biophysical methods for measuring skin hydration have varying degrees of correlation with one another, they also provide comparatively unique information about different regions within the SC. This should enable a more informed approach to product development in the future.

Three stepwise pH progressions in stratum corneum for homeostatic maintenance of the skin

The stratum corneum is the outermost skin layer with a vital role in skin barrier function. It is comprised of dead keratinocytes (corneocytes) and is known to maintain its thickness by shedding cells, although, the precise mechanisms that safeguard stratum corneum maturation and homeostasis remain unclear. Previous ex vivo studies have suggested a neutral-to-acidic pH gradient in the stratum corneum. Here, we use intravital pH imaging at single-corneocyte resolution to demonstrate that corneocytes actually undergo differentiation to develop three distinct zones in the stratum corneum, each with a distinct pH value. We identified a moderately acidic lower, an acidic middle, and a pH-neutral upper layer in the stratum corneum, with tight junctions playing a key role in their development. The upper pH neutral zone can adjust its pH according to the external environment and has a neutral pH under steady-state conditions owing to the influence of skin microbiota. The middle acidic pH zone provides a defensive barrier against pathogens. With mathematical modeling, we demonstrate the controlled protease activation of kallikrein-related peptidases on the stratum corneum surface that results in proper corneocyte shedding in desquamation. This work adds crucial information to our understanding of how stratum corneum homeostasis is maintained.

Film-Forming, Moisturizing, and Sensory Properties of a Cosmetic Formulation Containing Tara Gum and Brazilian Berry Extracts.

The development of cosmetic formulations with moisturizing and film-forming properties has been very important to help keep skin physiology and protection. In this context, this study aimed to develop a cosmetic formulation containing Tara gum and Brazilian berry extract and evaluate its physical-mechanical, film-forming, and sensory properties. A gel formulation was developed based on Tara gum added to Plinia cauliflora extract and was characterized by its spreadability profile and sensory properties. A clinical study was carried out with ten participants to evaluate the skin microrelief, stratum corneum water content, transepidermal water loss (TEWL), and skin morphological characteristics by reflectance confocal microscopy (RCM) before and after 2h of application of the formulations. The formulation with Brazilian berry significantly decreased the work of shear parameter, which can be correlated with improved spreadability in the sensory analysis. The clinical study showed that both formulations improved skin hydration and reduced the TEWL. The RCM imaging analysis showed the visible film on the skin surface, a decrease in the size of furrows, an increase in the reflectance of the interkeratinocytes, and reflectance of the stratum corneum for both formulations. These results were more pronounced for the formulation containing Brazilian berry. The Tara gum in the gel formulation promoted the formation and visualization of a polymeric net on the stratum corneum surface, demonstrated by the images obtained from RCM. However, the formulation added with the Brazilian berry extract improved the skin microrelief, honeycomb pattern of the epidermis, and skin hydration in deeper layers of the epidermis.

The implications of lipid mobility, drug-enhancers (surfactants)-skin interaction, and TRPV1 activation on licorice flavonoid permeability.

Licorice flavonoids (LFs) are derived from perennial herb licorice and have been attaining a considerable interest in cosmetic and skin ailment treatments. However, some LFs compounds exhibited poor permeation and retention capability, which restricted their application. In this paper, we systematically investigated and compared the enhancement efficacy and mechanisms of different penetration enhancers (surfactants) with distinct lipophilicity or "heat and cool" characteristics on ten LFs compounds. Herein, the aim was to unveil how seven different enhancers modified the stratum corneum (SC) surface and influence the drug-enhancers-skin interaction, and to relate these effects to permeation enhancing effects of ten LFs compounds. The enhancing efficacy was evaluated by enhancement ratio (ER)permeation, ERretention, and ERcom, which was conducted on the porcine skin. It was summarized that heat capsaicin (CaP) and lipophilic Plurol® Oleique CC 497 (POCC) caused the most significance of SC lipid fluidity, SC water loss, and surface structure alterations, thereby resulting in a higher permeation enhancing effects than other enhancers. CaP could completely occupied drug-skin interaction sites in the SC, while POCC only occupied most drug-skin interactions. Moreover, the enhancing efficacy of both POCC and CaP was dependent on the log P values of LFs. For impervious LFs with low drug solubility, enhancing their drug solubility could help them permeate into the SC. For high-permeation LFs, their permeation was inhibited ascribed to the strong drug-enhancer-skin strength in the SC. More importantly, drug-surfactant-skin energy possessed a good negative correlation with the LFs permeation amount for most LFs molecules. Additionally, the activation of transient receptor potential vanilloid 1 (TRPV1) could enhance LFs permeation by CaP. The study provided novel insights for drug permeation enhancement from the viewpoint of molecular pharmaceutics, as well as the scientific utilization of different enhancers in topical or transdermal formulations.

Influence of tissue desiccation on critical temperature for thermal damage during Er:YAG laser skin treatments.

Erbium lasers have become an accepted tool for performing both ablative and non-ablative medical procedures, especially when minimal invasiveness is desired. Hard-tissue desiccation during Er:YAG laser procedures is a well-known phenomenon in dentistry, the effect of which is to a certain degree being addressed by the accompanying cooling water spray. The desiccation of soft tissue has attracted much less attention due to the soft tissue's high-water content, resulting in a smaller effect on the ablation process. In this study, the characteristics of skin temperature decay following irradiations with Er:YAG laser pulses were measured using a fast thermal camera. The measurements revealed a substantial increase in temperature decay times and resulting thermal exposure times following irradiations with Er:YAG pulses with fluences below the laser ablation threshold. Based on an analytical model where the skin surface cooling time is calculated from the estimated thickness of the heated superficial layer of the stratum corneum (SC), the observed phenomena is attributed to the accelerated evaporation of water from the SC's surface. By using an Arrhenius damage integral-based variable heat shock model to describe the dependence of the critical temperature on the duration of thermal exposure, it is shown that contrary to what an inexperienced practitioner might expect, the low-to-medium level fluences may result in a larger thermal damage in comparison to treatments where higher fluences are used. This effect may be alleviated by hydrating the skin before Er:YAG treatments. Our study indicates that tissue desiccation may play a more important role than expected for soft-tissue procedures. It is proposed that its effect may be alleviated by hydrating the skin before Er:YAG treatments.

A sequential tape stripping approach for the assessment of the impact of personal cleansing products on the stratum corneum surface layers' acid mantle properties and antimicrobial defense.

Stratum corneum (SC) plays a critical role in skin barrier function for protection and defense in nature. The acidic skin pH, which is also known as the acid mantle, is very important in fighting against outer environmental threats, especially, bacteria. Furthermore, recent research has shown that the transient bacteria could potentially penetrate into deeper layer of the SC down to a few micrometers while posing an additional threat to the deeper layers of the skin. To develop a sequential tape stripping method for assessing the impact of personal cleansing product on the SC surface layers' acid mantle properties and antimicrobial defense against transient bacteria. Fifty-five subjects were recruited. High pH soap-based Product 1 and low pH synthetic surfactant-based Product 2 were applied on the left and right forearms of each subject. Sequential tape stripping was performed on the same spots to access multiple layers of the skin SC. Both antimicrobial defense property and skin pH of different skin layers were evaluated at baseline and 12 h after treatment. The skin's antimicrobial defense was significantly higher 12 h after treatment of the low pH Product 2 as compared to the treatment of high pH Product 1. In fact, this trend was consistent across all three skin layers (Layer 1 to Layer 3) as measured in this study (p < 0.01). Furthermore, the skin surface pH of Layer 1 and Layer 3 were also lower 12 h after the treatment of low pH Product 2 as compared to that of the high pH Product 1 (p < 0.01). The results of this investigation demonstrated the benefits of 12-h long lasting and deeper protection of SC acid mantle properties and antimicrobial defense using a low pH skin cleansing product as compared to a high pH product.

Carbon dioxide foam bubbles enhance skin penetration through the stratum corneum layer with mechanical mechanism

Topical skin formulations often include penetration enhancers that interact with the outer stratum corneum (SC) layer to chemically enhance diffusion. Alternatively, penetration can be mechanically enhanced with simple rubbing in the presence of solid particles sometimes included to exfoliate the top layers of the SC. Our goal was to evaluate micron-sized carbon dioxide bubbles included in a foamed moisturizing formulation as a mechanical penetration enhancement strategy. We show that moisturizing foam bubbles cause an increase in SC formulation penetration using both mechanical and spectroscopic characterization. Our results suggest viscous liquid film drainage between coalescing gaseous bubbles creates local regions of increased hydrodynamic pressure in the foam liquid layer adjacent to the SC surface that enhances treatment penetration. An SC molecular diffusion model is used to rationalize the observed behavior. The findings indicate marked increased levels of treatment concentration in the SC at 2 h and that persists to 18 h after exposure, far exceeding non-foamed treatments. The study suggests an alternate strategy for increasing formulation penetration with a non-chemical mechanism.

Hyaluronic acid and HA-modified cationic liposomes for promoting skin penetration and retention

Hyaluronic acid (HA) has been widely used in cosmetics and topical preparations owing to its favorable moisturizing property and potential in enhancing drugs' skin permeability. Here, the influencing factors and underlying mechanism of HA on skin penetration were carefully investigated, and HA-modified Undecylenoyl-Phenylalanine (UP) liposomes (HA-UP-LPs) were designed as a proof of principle for efficacious transdermal drug delivery strategy to enhance the skin penetration and retention. An in vitro penetration test (IVPT) of HA with different molecular weights showed that low molecular weight HA (LMW-HA, 5 kDa and 8 kDa) could pass through the stratum corneum (SC) barrier and enter into the epidermis and dermis layers, whereas its high molecular counterparts (HMW-HA) were trapped on the SC surface. Mechanistic studies revealed that LMW-HA could interact with keratin and lipid in the SC meanwhile exerted a substantial skin hydration effect, which may partially contribute to the SC penetration benefit. In addition, the surface decoration of HA drove an energy-dependent caveolae/lipid raft-mediated endocytosis of the liposomes through direct binding to the CD44 receptors widely expressed on skin cell membranes. Notably, IVPT showed a 1.36-fold and 4.86-fold increase in skin retention of UP and a 1.62-fold and 5.41-fold increase in skin penetration of UP with HA-UP-LPs over UP-LPs and free UP at 24 h, respectively. As a result, the anionic HA-UP-LPs (−30.0 mV) showed enhanced drug skin penetration and retention compared with conventional cationic bared UP-LPs (+21.3 mV) on both in vitro mini-pig skin as well as in vivo mouse skin. Overall, the usage of LMW-HA might offer opportunities in developing novel topical preparations and skin care products with improved transdermal penetration and retention.

A controlled forearm washing ex vivo method for assessing the impact of personal cleansing products on skin's acid mantle properties and antimicrobial defence against transient bacteria.

An important trend in the personal care industry involves the development of advanced personal cleaning products that not only provide skin mildness but support skin's acid mantle properties and skin's natural antimicrobial defence function. The objective of this study was to develop a controlled forearm washing ex vivo method for assessing the impact of personal cleansing products on skin's acid mantle properties and antimicrobial defence against transient bacteria. We developed a controlled forearm washing ex vivo method (ex vivo NET method) to compare the impact of two representative personal cleansing products on skin's acid mantle properties and antimicrobial defence against transient bacteria: one was a low-pH skin cleanser, and the other was high-pH soap cleanser. Skin pH was measured at baseline and 4 h after the product application. Concurrently, D-squame tape stripping procedure was followed to sample the stratum corneum surface layers. Then, two selected transient bacteria, Staphylococcus aureus and Escherichia coli, were inoculated onto the D-squame tapes and incubated under controlled conditions, respectively. The residual bacteria counts can provide an objective measure of skin's acid mantle properties against transient bacteria. Results from the ex vivo NET method were compared with the traditional in vivo cup-scrub RET method. The skin pH was significantly lower 4 h after washing the forearm with the low-pH cleanser versus the high-pH soap, consistent with literatures. Interestingly, the skin surface washed by the low-pH cleanser showed significantly higher hostility against representative transient bacteria as demonstrated by the lower counts of S. aureus by 1.09 log and E. coli by 0.6 log versus the high-pH soap based on the ex vivo NET method. Results from the ex vivo NET method were further supported by the traditional in vivo RET method which also showed the skin washed by the low-pH cleanser had significantly lower counts of S. aureus and E. coli versus the high-pH soap. The skin's acid mantle properties and antimicrobial defence can be directly impacted by the personal cleansing products. The low-pH skin cleanser works better than the high-pH soap for supporting skin's acid mantle properties and antimicrobial defence against transient bacteria. Results from the ex vivo NET method are consistent with the in vivo RET method. It is important that the ex vivo NET method offers many advantages since it is quicker to run with higher throughput and has better safety without the constraint of inoculating harmful microorganisms onto the human subjects.

How do the skin barrier and microbiome adapt to the extra-uterine environment after birth? Implications for the clinical practice.

The multiple protective functions of the skin derive from the interactions between epithelial skin and immune cells as well as the commensal microbiota. Developed in the last trimester of intra-uterine life, the skin barrier adapts dynamically after birth. Specific differences in the structure and physiology have been disclosed between infant and adult skin. The stratum corneum of infants is thinner and structured by thicker corneocytes with a more anisotropic surface in comparison to adult skin. Lower levels of the natural moisturizing factor and its constituents, together with the increased protease activity in the epidermis result in dry baby skin and ongoing adaptation of the desquamation to the extra-uterine environment. Infant epidermis is characterized by an accelerated proliferation rate and clinically competent permeability barrier in term neonates, despite the higher baseline values of transepidermal water loss in infants. The skin surface of newborns is less acidic, which could increase susceptibility to diaper and atopic dermatitis. Immediately after birth, skin is colonized by commensal bacteria-a process dependent on the mode of delivery and of major importance for the maturation of the immune system. Skin bacterial diversity and dysbiosis have been related to different pathology such as atopic and seborrheic dermatitis. This paper focuses on the ongoing structural, functional and biochemical adaptation of the human skin barrier after birth. We discuss the interactions on the 'skin barrier/ microbiota/ immune system' axis and their role in the development of competent functional integrity of the epidermal barrier.

Dynamics of post-occlusion water diffusion in stratum corneum

Diffusion of water through membranes presents a considerable challenge, as the diffusivity often depends on the local concentration of water. One particular example with strong biological relevance is the stratum corneum (SC) as the primary permeability barrier for the skin. A simple alternative for the constant diffusivity model is provided by the Fujita’s two-parameter rational approximation, which captures the experimentally observed fact that the SC diffusion constant for water increases with increasing the water concentration. Based on Fick’s law of diffusion, a one-dimensional concentration-dependent diffusion model is developed and applied for the analysis of both the steady-state transepidermal water loss (TEWL) and the non-steady-state so-called skin surface water loss (SSWL) occurred after removal of an occlusion patch from the SC surface. It is shown that some of the age-related changes in the SSWL can be qualitatively explained by the variation of the dimensionless Fujita concentration-dependence parameter.

Quantitative determination of concentration profiles of skin components and topically applied oils by tailored multivariate curve resolution-alternating least squares using in vivo confocal Raman micro-spectroscopy.

The main components of the stratum corneum (SC), water, lipids, and proteins, are non-homogeneously distributed throughout the depth. The quantitative determination of their concentration profiles and penetration depth of topically applied substances are urgent topics of dermatological and cosmetic research. Confocal Raman micro-spectroscopy has distinct advantages when determining semi-quantitative concentrations of SC components and topically applied substances non-invasively and in vivo. In this work, we applied a tailored multivariate curve resolution-alternating least squares (tMCR-ALS) method to analyze Raman spectra of the SC in the 2000-4000 cm-1 region for quantitatively determining the concentrations of water, lipids, proteins, and topically applied oils using substance-related spectral loadings which were allowed to change depth-dependently from the SC's surface toward its bottom. tMCR-ALS makes matching of depth-dependent signal attenuation, that is, the normalization on keratin, unnecessary and requires only a few additional experiments for calibration - Raman spectra of the pure materials and their densities.

410 Three stepwise pH zones to form functional stratum corneum

Stratum corneum (SC) is the outermost layer of the epidermis, which consists of nonviable anuclear keratinocytes (corneocytes) and function as a protective skin barrier. The pH distribution of SC has long been considered to impact its homeostasis. However, pH distribution and its biological significance in SC homeostasis remain unclear due to challenges in measuring and visualizing pH at a single-corneocyte resolution and elucidating the biological significance of pH profiles in SC. To tackle these challenges, we generated mice expressing Venus–mCherry, the fusion protein of pH-sensitive probe Venus and pH-insensitive probe mCherry from the uppermost stratum granulosum cells (SASP-Venus-mCherry mice), which enables the observation of relative pH changes and calculation of pH values via simultaneous ratiometric imaging. Confocal microscopic analysis of SASP-Venus-mCherry mice revealed that the SC has three stepwise pH zones, lower-moderately acidic (pH 6.0), middle-acidic (pH 5.4), and upper-nearly neutral (pH 6.7) zones, rather than gradual change over SC layers, in various body parts. Topical application of phosphate buffers with pH 4.1, 5.3, 6.4 and 7.2 did not affect pH of lower and middle SC-pH zones, while it changed pH of upper SC-pH zone according to the applied buffer. Additionally, the lower and middle SC-pH zones were dependent on claudin-1, a tight junction protein, which diminished in claudin-1-deficient mice; thus, the entire SC exhibits neutral pH. Finally, mathematical modeling demonstrated that the stepwise SC-pH profile pH6.0–pH5.4–pH6.7, but not the gradient SC-pH profile pH7–pH5 reproduced the increase of effective catalytic activity of kallikrein-related peptidases toward the SC surface. Collectively, these findings indicate that the three stepwise SC-pH zones are tightly regulated and are necessary to mediate adequate desquamation, which leads to functional SC differentiation.

Oxidative stress in the skin: Impact and related protection.

Skin, our first interface to the external environment, is subjected to oxidative stress caused by a variety of factors such as solar ultraviolet, infrared and visible light, environmental pollution, including ozone and particulate matters, and psychological stress. Excessive reactive species, including reactive oxygen species and reactive nitrogen species, exacerbate skin pigmentation and aging, which further lead to skin tone unevenness, pigmentary disorder, skin roughness and wrinkles. Besides these, skin microbiota are also a very important factor ensuring the proper functions of skin. While environmental factors such as UV and pollutants impact skin microbiota compositions, skin dysbiosis results in various skin conditions. In this review, we summarize the generation of oxidative stress from exogenous and endogenous sources. We further introduce current knowledge on the possible roles of oxidative stress in skin pigmentation and aging, specifically with emphasis on oxidative stress and skin pigmentation. Meanwhile, we summarize the science and rationale of using three well-known antioxidants, namely vitamin C, resveratrol and ferulic acid, in the treatment of hyperpigmentation. Finally, we discuss the strategy for preventing oxidative stress-induced skin pigmentation and aging.

Microscopic imaging of bronchoalveolar fluids of COVID-19 positive intubated patients reveals the different level of SARS-CoV-2 infection on oral squamosal epithelial cells

COVID-19 pandemic has been a global health emergency due to its association with severe pneumonia and high rate of mortality. In the current study, we reported the direct evidence for the variable level of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection on several types of oral epithelial cells isolated from the aspirated oropharyngeal and bronchoalveolar secretions of severely infected and intubated patients using cytology, confocal based immunofluorescence imaging (IF), scanning electron microscope (SEM) and transmission electron microscopic (TEM) studies. Cytological analysis showed the presence of keratinised and non-keratinised oral epithelial cells with viral inclusion bodies in stratum granulosum and intermedium cells. IF imaging using SARS-CoV-2 spike protein specific antibody confirmed the presence of virus inside the stratum spinosum/granulosum (keratinised) and stratum intermedium/superficial cells (non-keratinised). No SARS-CoV-2 viruses were seen in stratum corneum cells. SEM analysis also confirms the absence of virus like structure on stratum corneum surface while viruses like structure were seen on the stratum spinosum/granulosum/stratum/intermedium and stratum superficial cells. This advanced microscopic study confirms directly that the virus tends to infect and multiply in the metabolically active or sub-basal cells of oral epithelium and absent in the inactive keratinised stratum corneum from shedding zones of oral mucosa.

Guinea pig seborrheic dermatitis model of Malassezia restricta and the utility of luliconazole.

Seborrheic dermatitis (SD) is a multifactorial disease in which Malassezia restricta has been proposed as the predominant pathogenic factor. However, experimental evidence supporting this hypothesis is limited. A guinea pig SD model using a clinical isolate of M. restricta was used to elucidate the pathogenicity of M. restricta. Also, the efficacy of 1% luliconazole (LLCZ) cream, a topical imidazole derivative, against M. restricta was compared with that of a 2% ketoconazole (KCZ) cream in the same guinea pig model. Dorsal skin hairs of guinea pig were clipped and treated with M. restricta by single or repeated inoculations without occlusion. Skin manifestations were examined macroscopically and histologically. A quantitative polymerase chain reaction (PCR) assay was also performed for mycological evaluation. An inflammatory response mimicking SD occurred after repeated as well as single inoculation but not in abraded skin. The inflammation score attained its maximum on day 11 and persisted until day 52. The yeast form of the fungal elements was distributed on the surface of stratum corneum and around the follicular orifices, and an epidermal and dermal histological reaction was observed. Application of 1% LLCZ or 2% KCZ cream significantly improved the skin manifestations and decreased the quantity of M. restricta rDNA in the skin lesions. The efficacy of topical antifungal drugs suggested that M. restricta is a pathogenic factor contributing to SD.

Effects of Imprinted 3D Surface Patterning on Localized Changes in the Tribology of Human Stratum Corneum.

Natural surfaces may exhibit remarkable surface properties due to their structure. In the case of skin, its surface topography (microrelief) influences many of its perceived sensorial properties (shine, color, touch). Imprinted patterns can modify the original microrelief, inducing a completely new set of perceived properties. To explore the effects of superimposed biomimetic surface textures on the friction of skin, human stratum corneum was prepared with and without an imprinted regular, micrometer-sized, 3D grid pattern. Atomic Force Microscopy (AFM) and optical profilometry indicated that the inherent, smaller-scale roughness of the stratum corneum remained when lines with heights of 20-200 μm and spacings of 600-2000 μm were introduced, but it was somewhat reduced on the grid lines. Surface Forces Apparatus (SFA) friction experiments on stratum corneum were performed at low speed (μm/s, back-and-forth sliding) and at more realistic, high speed (cm/s, rotational sliding). Two stratum corneum surfaces in contact did not adhere to one another, and they had a friction coefficient μ of 0.1, or lower, at low sliding speed. An interesting loading-unloading hysteresis was observed, with lower friction force on unloading, in particular, when the contact was on a grid line of the patterned samples. This suggests that the patterning locally induced different mechanical properties of the stratum corneum and that its recovery was not immediate on unloading. When one stratum corneum surface slid against a rigid glass surface, the friction coefficient was always higher than that when two stratum corneum surfaces were in contact. At high sliding speed, much higher friction coefficients were found between one stratum corneum surface and a rigid, smooth surface, μ ≥ 1. The results demonstrate that topograpic patterning by imprinting clearly modifies the tribological response of stratum corneum. This approach provides a simple method for exploring the development of biomimetic modifications of skin texture.

Importance of the formulation in the skin delivery of topical diclofenac: not all topical diclofenac formulations are the same.

Purpose: The current study aimed to compare 2 topical diclofenac products (diclofenac diethylamine [DEA] 1.16% emulsion and diclofenac sodium [Na] 5% gel). The quantitative evaluation of skin permeability and the qualitative evaluation of their physical characteristics were performed.Methods: The skin permeability of diclofenac DEA 1.16% emulsion and diclofenac Na 5% gel was compared in vitro using Franz diffusion cells following a single, fixed, 10 mg/cm2 dose of product applied to a 0.64 cm2 area of the stratum corneum surface of ex vivo human skin samples. The physical characteristics of the 2 formulations were assessed by rheological measurement and microscopy observation.Results: Diclofenac DEA 1.16% emulsion exhibited a statistically significant higher permeation through human skin at 24 hrs than diclofenac Na 5% gel (554 vs 361 ng/cm2, respectively; ratio of adjusted geometric means, 1.54 [95% CI, 1.14–2.07]). When expressed as a percentage of the applied dose of diclofenac that permeated through human skin, a 7-fold difference was observed between the diclofenac DEA 1.16% emulsion (0.54%) and the diclofenac Na 5% gel (0.077%). Qualitative composition and physical characterization showed differences between the formulations that may explain some of the permeation data observed. Based on rheological assessments, diclofenac Na 5% gel had a higher viscosity (24.82 Pa.s) than diclofenac DEA 1.16% emulsion (10.29 Pa.s).Conclusion: A topical diclofenac product with a higher concentration of the active ingredient does not necessarily lead to greater absorption relative to a product with lower concentration of the active ingredient but different characteristics. These observations highlight the importance of considering parameters beyond drug concentration, such as composition, which may influence the solubility of the drug and permeation of topical nonsteroidal anti-inflammatory drugs.

Anisotropic cellular forces support mechanical integrity of the Stratum Corneum barrier

The protective function of biological surfaces that are exposed to the exterior of living organisms is the result of a complex arrangement and interaction of cellular components. This is the case for the most external cornified layer of skin, the stratum corneum (SC). This layer is made of corneocytes, the elementary ‘flat bricks’ that are held together through adhesive junctions. Despite the well-known protective role of the SC under high mechanical stresses and rapid cell turnover, the subtleties regarding the adhesion and mechanical interaction among the individual corneocytes are still poorly known. Here, we explore the adhesion of single corneocytes at different depths of the SC, by pulling them using glass microcantilevers, and measuring their detachment forces. We measured their interplanar adhesion between SC layers, and their peripheral adhesion among cells within a SC layer. Both adhesions increased considerably with depth. At the SC surface, with respect to adhesion, the corneocyte population exhibited a strong heterogeneity, where detachment forces differed by more than one order of magnitude for corneocytes located side by side. The measured detachment forces indicated that in the upper-middle layers of SC, the peripheral adhesion was stronger than the interplanar one. We conclude that the stronger peripheral adhesion of corneocytes in the SC favors an efficient barrier which would be able to resist strong stresses.

Impact of water exposure on skin barrier permeability and ultrastructure.

Skin occlusion caused by the use of diapers or sanitary napkins often results in irritant contact dermatitis. Furthermore, prolonged occlusion and exposure to body fluids are known to increase skin hydration and permeability, thus leading to irritant contact dermatitis. To investigate the effects of water exposure on the skin and its barrier functions, in order to obtain more insights into the mechanisms of irritant contact dermatitis. Water patches were applied to the volar forearm skin of 10 human subjects for 3 hours. Permeability of the stratum corneum (SC) was examined with methyl nicotinate (MN). Alterations in the hydration and ultrastructure of the SC were measured with Raman spectroscopy and multiphoton microscopy, respectively. Water profiles found with Raman spectroscopy showed notable increases in water content throughout the SC and skin surface. Multiphoton microscopy showed morphological changes in the intercellular space of the SC. Emerged pools seemed to contribute to increased MN absorption. Excessive skin hydration leading to changes in the SC ultrastructure might result in increased skin permeability to skin irritants and allergens.