OBJECTIVE:The aryl hydrocarbon receptor (AHR) is a regulator of epidermal homeostasis and a promising target for cosmetic and dermatological ingredients aimed at improving skin barrier function and reducing inflammation. This study investigated the potential of the natural polyphenol trans-resveratrol (RSV), a compound of cosmetic interest, to modulate downstream AHR signalling and restore epidermal integrity in a model of skin compromised by a pro-inflammatory environment. METHODS:A reconstructed human epidermis (RhE) was exposed to a cytokine cocktail (IL-4, IL-13, TNF-α) to induce a phenotype mimicking some aspects of atopic eczema, namely inflammation, oxidative stress and barrier disruption, features also prevalent in sensitive and reactive skin conditions. The effects of RSV were evaluated by assessing inflammatory mediators, oxidative stress-related markers, aryl hydrocarbon receptor signalling and epidermal barrier-associated proteins using molecular, biochemical and histological analyses. RESULTS:Cytokine exposure induced a pronounced inflammatory response, activation of aryl hydrocarbon receptor signalling, oxidative stress-related gene expression and dysregulation of barrier-related markers. Treatment with RSV attenuated the inflamed phenotype by reducing IL1A mRNA expression and IL-1α secretion, attenuating oxidative stress-associated AHR target gene responses through downregulation of CYP1A1 and CYP1B1, while maintaining AHR and HMOX1 expression and modulating barrier-associated gene expression, particularly by downregulating CASP14 and upregulating the tight junction protein occludin (OCLN). CONCLUSION:These findings provide mechanistic evidence in a human epidermis model that RSV can counteract inflammation, mitigate oxidative stress and support epidermal barrier homeostasis, actions mediated, at least in part, through modulation of AHR downstream signalling. This supports the potential of resveratrol as a multifunctional active ingredient in cosmetic and dermatological formulations designed to strengthen the skin barrier and calm sensitive or compromised skin.

Silicones are key ingredients in cosmetic products. Thanks to their unique chemistry and properties, silicones bring a large variety of functional benefits in almost all categories of cosmetic products and formats. This chapter provides an updated overview related to the usage of silicone technologies in skin care, sun care, color cosmetics, hair care, and AP-Deo products. Silicones were introduced in the cosmetic industry in the 1950s to prevent the soaping effect of soap-based skin care lotions. Today, more than 30% of all new products launched on the market at a global level contain silicones. Often used for the sensorial benefits, silicones improve the performance of cosmetic formulations by offering long-lasting benefits, formulation flexibility, and protection benefits.

The stratum corneum (SC) acts as the main barrier of the skin against exogenous substances (e.g. air pollutants) and against the loss of endogenous substances such as water. The SC consists of keratin-rich dead cells surrounded by crystalline lamellar lipid regions. The main lipid classes are ceramides (CERs), free fatty acids (FFAs), and cholesterol (CHOL). Tropospheric ozone (O3) is a potent oxidant compound that reacts instantly with biological molecules such as lipids and proteins. Although it has been reported that O3 induces biological responses at the cellular level, to the best of our knowledge, there is no information related to the damages O3 can cause at the level of the SC extracellular lipid matrix. The aim of our work was to investigate which SC lipid subclasses are prone to oxidation when exposed to O3 and how the changes in chemical structures affect the lipid organization in a stratum corneum substitute (SCS) membrane. Ultimately, the barrier properties of the SCS were examined. Our studies revealed that O3 induces chemical modifications of the unsaturated bonds in CERs and CHOL. The appearance of carbonyl groups at the headgroup level and the removal of the linoleate moiety of omega‑O‑acylceramides (CER EOS) impact the lamellar organization of the lipid assembly and to a lesser extent the lateral packing of the lipids. Unexpectedly, these changes improved the barrier function of the SCS.

A three-dimensional human epidermis model reconstructed from neonatal primary keratinocytes is presented. Herein, a protocol for the cultivation process and the characterization of the model is described. Neonatal primary keratinocytes are grown submerged on permeable polycarbonate inserts and lifted to the air-liquid interface three days after seeding. After fourteen days of stimulation with defined growth factors and ascorbic acid in high calcium culture medium, the model is fully differentiated. Histological analysis revealed a completely stratified epidermis, mimicking the morphology of native human skin. To characterize the model and its barrier functions, protein levels and localization specific for early-stage keratinocyte differentiation (i.e., keratin 10), late-stage differentiation (i.e., involucrin, loricrin, and filaggrin) and tissue adhesion (i.e., desmoglein 1), were assessed by immunofluorescence. The tissue barrier integrity was further evaluated by measuring transepithelial electrical resistance. Reconstructed human epidermis was responsive to proinflammatory stimuli (i.e., lipopolysaccharide and tumor necrosis factor alpha), leading to increased cytokine release (i.e., interleukin 1 alpha and interleukin 8). This protocol represents a straightforward and reproducible in vitro method to cultivate reconstructed human epidermis as a tool to assess environmental effects and a broad range of skin-related studies.

Cigarette smoke stands among the most toxic environmental pollutants and is composed of thousands of chemicals including polycyclic aromatic hydrocarbons (PAHs). Despite restrict cigarette smoking ban in indoor or some outdoor locations, the risk of non-smokers to be exposed to environmental cigarette smoke is not yet eliminated. Beside the well-known effects of cigarette smoke to the respiratory and cardiovascular systems, a growing literature has shown during the last 3 decades its noxious effects also on cutaneous tissues. Being the largest organ as well as the interface between the outer environment and the body, human skin acts as a natural shield which is continuously exposed to harmful exogenous agents. Thus, a prolonged and/or repetitive exposure to significant levels of toxic smoke pollutants may have detrimental effects on the cutaneous tissue by disrupting the epidermal barrier function and by exacerbating inflammatory skin disorders (i.e. psoriasis, atopic dermatitis). With the development of very complex skin tissue models and sophisticated cigarette smoke exposure systems it has become important to better understand the toxicity pathways induced by smoke pollutants in more realistic laboratory conditions to find solutions for counteracting their effects. This review provides an update on the skin models currently available to study cigarette smoke exposure and the known pathways involved in cutaneous toxicity. In addition, the article will briefly cover the inflammatory skin pathologies potentially induced and/or exacerbated by cigarette smoke exposure.

Being exposed to ground-level ozone (O3), as it is often the case in polluted cities, is known to have a detrimental impact on skin. O3 induces antioxidant depletion and lipid peroxidation in the upper skin layers and this effect has repercussions on deeper cellular layers, triggering a cascade of cellular stress and inflammatory responses. Repetitive exposure to high levels of O3 may lead to chronic damages of the cutaneous tissue, cause premature skin aging and aggravate skin diseases such as contact dermatitis and urticaria. This review paper debates about the most relevant experimental approaches that must be considered to gather deeper insights about the complex biological processes that are activated when the skin is exposed to O3. Having a better understanding of O3 effects on skin barrier properties and stress responses could help the whole dermato-cosmetic industry to design innovative protective solutions and develop specific cosmetic regime to protect the skin of every citizen, especially those living in areas where exposure to high levels of O3 is of concern to human health.

Background Air pollution is killing close to 5 million people a year, and harming billions more. Air pollution levels remain extremely high in many parts of the world, and air pollution-associated premature deaths have been reported for urbanized areas, particularly linked to the presence of airborne nano-sized and ultrafine particles. Main text To date, most of the research studies did focus on the adverse effects of air pollution on the human cardiovascular and respiratory systems. Although the skin is in direct contact with air pollutants, their damaging effects on the skin are still under investigation. Epidemiological data suggested a correlation between exposure to air pollutants and aggravation of symptoms of chronic immunological skin diseases. In this study, a systematic literature review was conducted to understand the current knowledge on the effects of airborne particulate matter on human skin. It aims at providing a deeper understanding of the interactions between air pollutants and skin to further assess their potential risks for human health. Conclusion Particulate matter was shown to induce a skin barrier dysfunction and provoke the formation of reactive oxygen species through direct and indirect mechanisms, leading to oxidative stress and induced activation of the inflammatory cascade in human skin. Moreover, a positive correlation was reported between extrinsic aging and atopic eczema relative risk with increasing particulate matter exposure.

This report demonstrates the benefits of silicone-based polymers for enhancing pharmaceutical drug delivery to skin, by means of three independent studies. The first revealed that an anhydrous semisolid formulation with a cross-linked silicone polymer offers faster and higher skin delivery of the nonsteroidal anti-inflammatory drug ibuprofen (IBP) compared to similar formulations based on organic excipients, as well as to a commercial benchmark. The second study focused on ascorbic acid (AA), a depigmenting agent used to treat hyperpigmentation disorders. This study combined a cross-linked silicone polymer and a silicone emulsifier to develop an anhydrous glycerinin-silicone system that stabilized AA for a significantly longer time compared to a commercial benchmark. Preservation of the chemical stability of the drug was shown to have a direct impact on its depigmenting activity. The third study focused on betamethasone dipropionate (BDP), a corticosteroid used to treat itching in chronic skin disorders. This study showed that a silicone resin crosspolymer film-forming emulsion provides significantly higher substantivity than a commercial benchmark based on an oil-inwater emulsion without impacting the delivery of BDP to skin.

Based on its outstanding antifungal properties, it is reasonable to believe that fengycin might be efficient to topically treat localized dermatomycoses. Since most of the fungi species involved in the formation of those mycotic skin diseases colonize primarily the stratum corneum (SC), studying the interaction between fengycin and SC-mimicking lipid membranes is a primary step to determine the potential of fengycin to overcome the physical barrier of the skin. In this respect, multilamellar lipid vesicles (MLVs), with a lipid composition mimicking that of the SC, were prepared and characterized by differential scanning calorimetry (DSC). The critical micelle concentration (CMC) of fengycin was also assessed under skin conditions and found to be 1.2 ± 0.1 μM. The molecular interactions of fengycin with SC-mimicking MLVs were investigated by both DSC and isothermal titration calorimetry (ITC). Results showed that the interactions were considerably affected by changes in lipid phase behaviour. At 40 °C and below, fengycin induced exothermic changes in the lipid structures suggesting that less-ordered lipid domains became more-ordered in presence of fengycin. At 60 °C, clearly endothermic interaction enthalpies were observed, which could arise from the "melting" of remaining solid domains enriched in high melting lipids that without fengycin melt at higher temperatures.

A sheet gelatin scaffold with attached silicone pseudoepidermal layer for wound repair purposes was produced by a cryogelation technique. The resulting scaffold possessed an interconnected macroporous structure with a pore size distribution of 131±17μm at one surface decreasing to 30±8μm at the attached silicone surface. The dynamic storage modulus (G′) and mechanical stability were comparable to the clinical gold standard dermal regeneration template, Integra®. The scaffolds were seeded in vitro with human primary dermal fibroblasts. The gelatin based material was not only non-cytotoxic, but over a 28day culture period also demonstrated advantages in cell migration, proliferation and distribution within the matrix when compared with Integra®. When seeded with human keratinocytes, the neoepidermal layer that formed over the cryogel scaffold appeared to be more advanced and mature when compared with that formed over Integra®. The in vivo application of the gelatin scaffold in a porcine wound healing model showed that the material supports wound healing by allowing host cellular infiltration, biointegration and remodelling. The results of our in vitro and in vivo studies suggest that the gelatin based scaffold produced by a cryogelation technique is a promising material for dermal substitution, wound healing and other potential biomedical applications.

Objectives Lipopeptides are compounds derived from microorganisms that exhibit pronounced surface and emulsifying activity. The ability of lipopeptides to interact with stratum corneum lipids makes them candidates as transdermal penetration enhancers. We have investigated the potential of two lipopeptides, fengycin and surfactin, to act as enhancers for the transdermal penetration and skin accumulation of aciclovir.Methods To investigate a possible synergistic effect, surfactin and fengycin were associated with anodal iontophoresis. Permeation experiments were performed using vertical diffusion cells and pig ear skin as barrier. Differential scanning calorimetry was used to study the interaction between fengycin and stratum corneum lipids.Key findings The results obtained indicated that surfactin and fengycin were not suitable to enhance aciclovir flux across the skin, not even when associated with iontophoresis. Aciclovir flux was slightly decreased in passive conditions and unchanged (fengycin) or decreased (surfactin) in anodal iontophoretic conditions. When applied in passive conditions, fengycin and surfactin increased aciclovir concentration in the epidermis by a factor of 2.Conclusions Surfactin and fengycin did not enhance aciclovir transport across the skin (not even when associated with iontophoresis) although they increased aciclovir concentration in the epidermis by a factor of 2.

Biological membranes play an essential role in the cellular protection as well as in the control and the transport of nutrients. Many mechanisms such as molecular recognition, enzymatic catalysis, cellular adhesion and membrane fusion take place into the biological membranes. In 1972, Singer et al. provided a membrane model, called fluid mosaic model, in which each leaflet of the bilayer is formed by a homogeneous environment of lipids in a fluid state including globular assembling of proteins and glycoproteins. Since its conception in 1972, many developments were brought to this model in terms of composition and molecular organization. The main development of the fluid mosaic model was made by Simons et al. (1997) and Brown et al. (1997) who suggested that membrane lipids are organized into lateral microdomains (or lipid rafts) with a specific composition and a molecular dynamic that are different to the composition and the dynamic of the surrounding liquid crystalline phase. The discovery of a phase separation in the plane of the membrane has induced an explosion in the research efforts related to the biology of cell membranes but also in the development of new technologies for the study of these biological systems. Due to the high complexity of biological membranes and in order to investigate the biological processes that occur on the membrane surface or within the membrane lipid bilayer, a large number of studies are performed using biomimicking model membranes. This paper aims at revisiting the fundamental properties of biological membranes in terms of membrane composition, membrane dynamic and molecular organization, as well as at describing the most common biomimicking models that are frequently used for investigating biological processes such as membrane fusion, membrane trafficking, pore formation as well as membrane interactions at a molecular level.

Three kinds of derivatives of the M(1) factor of virginiamycin have been synthesised: esters with long chain fatty acids, oximes with modified polar amino acids and bis-derivatives with both the ester and oxime function. The study of the surface tension time dependence of M(1) and its derivatives has shown that it is necessary to enhance simultaneously the hydrophobicity and the hydrophilicity of M(1) to render M(1) surface-active. A structure/function relationship study of the surface-active bis-derivatives has shown that enhancing the hydrophobicity of the molecule led to slower adsorption kinetics, higher stability of the monolayers formed and a better capacity to penetrate a membrane model. The repulsive electrostatic forces due to the presence of charges on the amino acids linked to M(1) lead to higher surface tensions, a greater molecular area at the interface and lower penetration into a membrane model. This study has demonstrated that modifying systematically the hydrophobicity and hydrophilicity of a non surface-active molecule allows the production of surface-active derivatives.

The combination of atomic force microscopy (AFM) and the Langmuir trough technique was used in this work to investigate the molecular interactions of fengycin with lipid monolayers constituted of the major lipid classes found in human stratum corneum (SC). AFM imaging of spread SC lipids/fengycin monolayers showed that fengycin preferentially partitions into cholesterol-rich phases surrounding 2D domains mainly constituted of ceramide and fatty acid molecules. Penetration experiments of fengycin from the subphase into SC-mimicking monolayers clearly indicated that the lipopeptide insertion at the lipid interface is enhanced in the presence of cholesterol. AFM analysis of mixed SC lipids/fengycin monolayers obtained after lipopeptide penetration revealed that cholesterol strongly interacts with fengycin and undergoes specific molecular interactions with more disordered, loosely packed ceramide molecules. These results highlight the capacity of fengycin to interact with the lipid constituents of the extracellular matrix of SC and, in particular, with cholesterol.

The effect of the environmental conditions both on the behaviour of fengycin at the air-aqueous interface and on its interaction with DPPC was studied using surface pressure–area isotherms and AFM. The ionisation state of fengycin is at the origin of its monolayer interfacial properties. The most organised interfacial arrangement is obtained when fengycin behaves as if having zero net charge (pH 2). In a fully ionised state (pH 7.4), the organisation and the stability of fengycin monolayers depend on the ionic strength in the subphase. This can modulate the surface potential of fengycin and consequently the electrostatic repulsions inside the interfacial monolayer, as well as the lipopeptide interaction with the layer of water molecules forming the air–water interface. Intermolecular interactions of fengycin with DPPC are also strongly affected by the ionisation state of lipopeptide and the surface pressure (Π) of the monolayer. A better miscibility between both interfacial components is observed at pH 2, while negatively charged lipopeptide molecules are segregated from the DPPC phase. A progressive desorption of fengycin from the interface is observed at pH 7.4 when Π increases while at pH 2, fengycin desorption brutally occurs when Π rises above Π value of the intermediate plateau.