Does sensitive skin lie in epidermal barrier impairment or abnormalities? Results from an observational study assessing biophysical parameters.

BACKGROUND: The pathophysiology of sensitive skin is largely unknown and no univocal data on the role of the epidermal barrier impairment have been identified. The aim of this study was to assess whether subjects with or without sensitive skin differ for some biophysical skin parameters, which reflect skin barrier integrity or skin hyperactivity. METHODS: This observational, cross-sectional study included adult volunteers not affected with chronic inflammatory skin diseases who attended the Unit of Dermatology and the Center of Cosmetology of the University of Ferrara, Ferrara, Italy, between March 2021 and November 2022. All subjects, subdivided into those with or without sensitive skin, based on either Lactic Acid Stinging Test (LAST) result or a questionnaire-based skin sensitivity score ≥4, were tested for transepidermal water loss (TEWL), skin elasticity and hydrations and dermographism. RESULTS: One hundred and eighty-seven subjects were included. No significant differences in terms of TEWL, elasticity and hydration levels were recorded between subjects with sensitive skin and those without, subdivided according to both the LAST result and the questionnaire score. Dermographism was elicited more in subjects with sensitive skin than in the others, although without statistical significance. CONCLUSIONS: The study failed to find significant biophysical differences between sensitive and non-sensitive skin. Therefore, the role of skin barrier impairment does not appear to be a necessary condition in determining an abnormal skin sensitivity to potentially unpleasant and irritating stimuli. These findings indirectly support the relevance of a peripheral sensory neural hyperactivity in the pathophysiology of sensitive skin.

Ethosomes for Curcumin and Piperine Cutaneous Delivery to Prevent Environmental-Stressor-Induced Skin Damage.

Diesel particulate matter is one of the most dangerous environmental stressors affecting human health. Many plant-derived compounds with antioxidant and anti-inflammatory properties have been proposed to protect the skin from pollution damage. Curcumin (CUR) has a plethora of pharmacological activities, including anticancer, antimicrobial, anti-inflammatory and antioxidant. However, it has low bioavailability due to its difficult absorption and rapid metabolism and elimination. CUR encapsulation in nanotechnological systems and its combination with biopotentiators such as piperine (PIP) can improve its pharmacokinetics, stability and activity. In this study, ethosomes (ETs) were investigated for CUR and PIP delivery to protect the skin from damage induced by diesel particulate matter. ETs were produced by different strategies and characterized for their size distribution by photon correlation spectroscopy, for their morphology by transmission electron microscopy, and for their drug encapsulation efficiency by high-performance liquid chromatography. Franz cells enabled us to evaluate in vitro the drug diffusion from ETs. The results highlighted that ETs can promote the skin permeation of curcumin. The studies carried out on their antioxidant activity demonstrated an increase in the antioxidant power of CUR using a combination of CUR and PIP separately loaded in ETs, suggesting their possible application for the prevention of skin damage due to exogenous stressors. Ex vivo studies on human skin explants have shown the suitability of drug-loaded ETs to prevent the structural damage to the skin induced by diesel engine exhaust exposure.

Lipid-Based Nanosystems for the Topical Application of Ferulic Acid: A Comparative Study.

In this study, we examined and compared two different lipid-based nanosystems (LBNs), namely Transferosomes (TFs) and Monoolein Aqueous Dispersions (MADs), as delivery systems for the topical application of Ferulic Acid (FA), an antioxidant molecule derived from natural sources. Our results, as demonstrated through Franz-cell experiments, indicate that the LBNs produced with poloxamer 188 in their composition create a multilamellar system. This system effectively controls the release of the drug. Nonetheless, we found that the type of non-ionic surfactant can impact the drug release rate. Regarding FA diffusion from the MAD, this showed a lower diffusion rate compared with the TF. In terms of an in vivo application, patch tests revealed that all LBN formulations tested were safe when applied under occlusive conditions for 48 h. Additionally, human skin biopsies were used to determine whether FA-containing formulations could influence skin tissue morphology or provide protection against O3 exposure. Analyses suggest that treatment with TFs composed of poloxamer 188 and MAD formulations might protect against structural skin damage (as observed in hematoxylin/eosin staining) and the development of an oxidative environment (as indicated by 4-hyroxinonenal (4HNE) expression levels) induced by O3 exposure. In contrast, formulations without the active ingredient did not offer protection against the detrimental effects of O3 exposure.Inizio modulo.

Niosomes for Topical Application of Antioxidant Molecules: Design and In Vitro Behavior.

In the present study, gels based on xanthan gum and poloxamer 407 have been developed and characterized in order to convey natural antioxidant molecules included in niosomes. Specifically, the studies were conducted to evaluate how the vesicular systems affect the release of the active ingredient and which formulation is most suitable for cutaneous application. Niosomes, composed of Span 20 or Tween 20, were produced through the direct hydration method, and therefore, borate buffer or a micellar solution of poloxamer 188 was used as the aqueous phase. The niosomes were firstly characterized in terms of morphology, dimensional and encapsulation stability. Afterwards, gels based on poloxamer 407 or xanthan gum were compared in terms of spreadability and adhesiveness. It was found to have greater spreadability for gels based on poloxamer 407 and 100% adhesiveness for those based on xanthan gum. The in vitro diffusion of drugs studied using Franz cells associated with membranes of mixed cellulose esters showed that the use of a poloxamer micellar hydration phase determined a lower release as well as the use of Span 20. The thickened niosomes ensured controlled diffusion of the antioxidant molecules. Lastly, the in vivo irritation test confirmed the safeness of niosomal gels after cutaneous application.

Ethosomal Gel for Topical Administration of Dimethyl Fumarate in the Treatment of HSV-1 Infections.

The infections caused by the HSV-1 virus induce lesions on the lips, mouth, face, and eye. In this study, an ethosome gel loaded with dimethyl fumarate was investigated as a possible approach to treat HSV-1 infections. A formulative study was conducted, evaluating the effect of drug concentration on size distribution and dimensional stability of ethosomes by photon correlation spectroscopy. Ethosome morphology was investigated by cryogenic transmission electron microscopy, while the interaction between dimethyl fumarate and vesicles, and the drug entrapment capacity were respectively evaluated by FTIR and HPLC. To favor the topical application of ethosomes on mucosa and skin, different semisolid forms, based on xanthan gum or poloxamer 407, were designed and compared for spreadability and leakage. Dimethyl fumarate release and diffusion kinetics were evaluated in vitro by Franz cells. The antiviral activity against HSV-1 was tested by plaque reduction assay in Vero and HRPE monolayer cells, while skin irritation effect was evaluated by patch test on 20 healthy volunteers. The lower drug concentration was selected, resulting in smaller and longer stable vesicles, mainly characterized by a multilamellar organization. Dimethyl fumarate entrapment in ethosome was 91% w/w, suggesting an almost total recovery of the drug in the lipid phase. Xanthan gum 0.5%, selected to thicken the ethosome dispersion, allowed to control drug release and diffusion. The antiviral effect of dimethyl fumarate loaded in ethosome gel was demonstrated by a reduction in viral growth both 1 h and 4 h post-infection. Moreover, the patch test demonstrated the safety of the ethosomal gel applied on the skin.

Results from an extended study on the reliability of a questionnaire for the diagnosis of sensitive skin: Confirmations and improvements.

OBJECTIVE: A recently proposed self-assessment questionnaire aimed at diagnosing sensitive skin provided promising results in a relatively small population. The main objectives were: (i) to assess the reliability of the aforementioned questionnaire in a larger population and verify the cut-off score previously found to predict skin sensitivity (defined as positivity to LAST, lactic acid stinging test) and (ii) to define a formula that yields the probability of a positive LAST result. METHODS: Adult volunteers were included in this observational, cross-sectional, extended study. Both LAST-positive subjects, who were considered as having sensitive skin ('patients') and negative ones ('controls') completed the questionnaire, which concerned sensitivity to possible triggers of unpleasant skin sensations in real life. A cumulative score (questionnaire-based skin sensitivity score, 0-10) was calculated from the sum of all items. RESULTS: Three hundred and sixty-four subjects were enrolled, 214 patients and 150 controls. The mean questionnaire-based skin sensitivity score was significantly higher among patients than controls. Using two different methods, cut-off values of 4 and 5 were defined for the identification of LAST-positive subjects, with 76.6% and 72.8% accuracy, respectively. Scores below 4 or above 5 showed a high (80% or better) negative or positive predictive value, respectively. The coefficients found that in multivariate analysis for each questionnaire item, gender and age allowed us to calculate the probability of LAST positivity with higher precision taking into account the 'relative weight' of each factor. CONCLUSION: With small variations in the results, the self-assessment questionnaire confirmed its reliability for diagnosing sensitive skin in clinical practice.

INTRODUCTION: Un questionnaire d'auto-évaluation récemment proposé visant à diagnostiquer la peau sensible a fourni des résultats prometteurs dans une population relativement petite. Les principaux objectifs étaient: (i) d'évaluer la fiabilité du questionnaire susmentionné dans une population plus large et de vérifier la valeur du cut-off précédemment trouvé pour prédire la sensibilité cutanée (définie comme la positivité au LAST, de l'anglais « test de piqûre d'acide lactique ¼), et (ii) de définir une formule qui donne la probabilité d'un résultat LAST positif. MÉTHODES: Des volontaires adultes ont été inclus dans cette étude observationnelle, transversale et étendue. Les sujets LAST-positifs, qui étaient considérés comme ayant la peau sensible ('patients'), et les sujets négatifs ('témoins') ont rempli le questionnaire, qui concernait la sensibilité aux possibles déclencheurs de sensations cutanées désagréables dans la vie réelle. Un score cumulatif (score de sensibilité cutanée basé sur un questionnaire, 0-10) a été calculé à partir de la somme de tous les éléments. RÉSULTATS: Trois cent soixante-quatre sujets ont été recrutés, 214 patients et 150 témoins. Le résultat moyen de sensibilité cutanée basé sur le questionnaire était significativement plus élevé chez les patients que chez les témoins. En utilisant deux méthodes différentes, des valeurs seuils de 4 et 5 ont été définies pour l'identification des sujets LAST-positifs, avec une précision de 76,6% et 72,8%, respectivement. Les scores inférieurs à 4 ou supérieurs à 5 ont montré une valeur prédictive négative ou positive élevée (80% ou plus), respectivement. Les coefficients trouvés en différentes analyses pour chaque élément du questionnaire, sexe et âge nous ont permis de calculer la probabilité de positivité LAST avec une plus grande précision en tenant compte du « poids relatif ¼ de chaque facteur. CONCLUSIONS: Avec de faibles variations dans les résultats, le questionnaire d'auto-évaluation a confirmé sa fiabilité pour le diagnostic des peaux sensibles dans la pratique clinique.

Dimethyl Fumarate-Loaded Transethosomes: A Formulative Study and Preliminary Ex Vivo and In Vivo Evaluation.

In this study, transethosomes were investigated as potential delivery systems for dimethyl fumarate. A formulative study was performed investigating the effect of the composition of transethosomes on the morphology and size of vesicles, as well as drug entrapment capacity, using cryogenic transmission electron microscopy, photon correlation spectroscopy, and HPLC. The stability of vesicles was evaluated, both for size increase and capability to control the drug degradation. Drug release kinetics and permeability profiles were evaluated in vitro using Franz cells, associated with different synthetic membranes. The in vitro viability, as well as the capacity to improve wound healing, were evaluated in human keratinocytes. Transmission electron microscopy enabled the evaluation of transethosome uptake and intracellular fate. Based on the obtained results, a transethosome gel was further formulated for the cutaneous application of dimethyl fumarate, the safety of which was evaluated in vivo with a patch test. It was found that the phosphatidylcholine concentration affected vesicle size and lamellarity, influencing the capacity to control dimethyl fumarate's chemical stability and release kinetics. Indeed, phosphatidylcholine 2.7% w/w led to multivesicular vesicles with 344 nm mean size, controlling the drug's chemical stability for at least 90 days. Conversely, phosphatidylcholine 0.9% w/w resulted in 130 nm sized unilamellar vesicles, which maintained 55% of the drug over 3 months. These latest kinds of transethosomes were able to improve wound healing in vitro and were easily internalised by keratinocytes. The selected transethosome gel, loading 25 mg/mL dimethyl fumarate, was not irritant after cutaneous application under occlusion, suggesting its possible suitability in the treatment of wounds caused by diabetes mellitus or peripheral vascular diseases.

Proposal of a self-assessment questionnaire for the diagnosis of sensitive skin.

BACKGROUND: Sensitive skin is very common and distressing. Its diagnosis may be difficult with the tools/methods available at the moment. AIMS: To assess the reliability of a self-assessment questionnaire for the diagnosis of sensitive skin, using the results of lactic acid stinging test (LAST) as a reference for the identification of subjects suffering from this condition. A further objective was to identify the questionnaire cutoff score that better discriminates between subjects with or without sensitive skin. PATIENTS/METHODS: Among the adult volunteers included in this observational, cross-sectional study, both LAST-positive subjects, who were considered as having sensitive skin ("patients"), and negative ones ("controls") completed the questionnaire. It consisted of a part for self-assessing and quantifying (0-10) sensitive skin and another one that included 10 items, each referring to a specific, potentially triggering stimulus. A cumulative score (questionnaire-based skin sensitivity score, 0-10) was calculated from the sum of all items considered capable of triggering unpleasant skin sensations in real-life experience. RESULTS: One hundred and sixty-two subjects were enrolled, 102 patients and 60 controls; 98 subjects thought they had sensitive skin. The mean questionnaire-based skin sensitivity score was significantly higher among patients than controls and correlated with skin sensitivity self-assessments. A cutoff value of 3 was set for the identification of LAST-positive subjects, with 79% accuracy. CONCLUSIONS: The study self-assessment questionnaire seems to be a reliable tool for diagnosing sensitive skin in clinical practice. These results led us to identify a numerical cutoff for detecting propensity to experience sensitive skin.

Mangiferin-Loaded Smart Gels for HSV-1 Treatment.

Infections due to HSV-1 affect many people all over the world. To counteract this pathology, usually characterized by perioral sores or by less frequent serious symptoms including keratitis, synthetic antiviral drugs are employed, such as acyclovir, often resulting in resistant viral strains under long-term use. Many plant-derived compounds, such as mangiferin and quercetin, have demonstrated antiviral potentials. In this study, smart semisolid forms based on phosphatidylcholine and Pluronic were investigated as delivery systems to administer mangiferin on skin and mucosae affected by HSV-1 infection. Particularly, lecithin organogels, Pluronic gel, and Pluronic lecithin organogels were formulated and characterized. After the selection of gel compositions, physical aspects, such as rheological behavior, spreadability, leakage, and adhesion were evaluated, suggesting a scarce suitability of the lecithin organogel for topical administration. Mangiferin was efficiently included in all type of gels. An in vitro study based on the Franz cell enabled us to find evidence of the gel capability to control drug diffusion, especially in the case of Pluronic organogel, while an in vivo study conducted on human volunteers demonstrated the safeness of all of the gels after cutaneous administration. Furthermore, a plaque reduction assay demonstrated the virucidal effect of mangiferin loaded in a Pluronic gel and a Pluronic lecithin organogel against the HSV-1 KOS strain.

The Potential of Caffeic Acid Lipid Nanoparticulate Systems for Skin Application: In Vitro Assays to Assess Delivery and Antioxidant Effect.

The object of this study is a comparison between solid lipid nanoparticles and ethosomes for caffeic acid delivery through the skin. Caffeic acid is a potent antioxidant molecule whose cutaneous administration is hampered by its low solubility and scarce stability. In order to improve its therapeutic potential, caffeic acid has been encapsulated within solid lipid nanoparticles and ethosomes. The effect of lipid matrix has been evaluated on the morphology and size distribution of solid lipid nanoparticles and ethosomes loaded with caffeic acid. Particularly, morphology has been investigated by cryogenic transmission electron microscopy and small angle X-ray scattering, while mean diameters have been evaluated by photon correlation spectroscopy. The antioxidant power has been evaluated by the 2,2-diphenyl-1-picrylhydrazyl methodology. The influence of the type of nanoparticulate system on caffeic acid diffusion has been evaluated by Franz cells associated to the nylon membrane, while to evaluate caffeic acid permeation through the skin, an amperometric study has been conducted, which was based on a porcine skin-covered oxygen electrode. This apparatus allows measuring the O2 concentration changes in the membrane induced by polyphenols and H2O2 reaction in the skin. The antioxidative reactions in the skin induced by caffeic acid administered by solid lipid nanoparticles or ethosomes have been evaluated. Franz cell results indicated that caffeic acid diffusion from ethosomes was 18-fold slower with respect to solid lipid nanoparticles. The amperometric method evidenced the transdermal delivery effect of ethosome, indicating an intense antioxidant activity of caffeic acid and a very low response in the case of SLN. Finally, an irritation patch test conducted on 20 human volunteers demonstrated that both ethosomes and solid lipid nanoparticles can be safely applied on the skin.