Influence of disease phase on embitterment and emotional dysregulation in psoriatic patients.

This study aimed to evaluate the psychosocial differences between patients with psoriasis in different phases of the disease. Seventy-one patients in exacerbation and 83 in remission were evaluated regarding sociodemographic, clinical and psychological variables, on the premise that the visibility of lesions (exacerbation phase) may impact the emotional regulation and embitterment. A regression analysis was performed to identify the variables that contribute to explain embitterment: a diagnosis of anxiety and/or depression and psoriasis severity are the identified ones. The results point to higher values of emotional dysregulation and embitterment, as well as more critical clinical variables in patients with active disease, namely, alcohol and coffee consumption, smoking and less satisfaction with current treatment, more diagnoses and more family history of anxiety and depression, more psychology/psychiatry consultations and more use of anxiolytics and antidepressants. However, only the results referring to alcohol consumption and embitterment are significantly higher in subjects in the exacerbation phase of the disease. Particular clinical attention should be provided to patients in exacerbation phase regarding psychotherapeutic approach.

Xanthones for melanogenesis inhibition: Molecular docking and QSAR studies to understand their anti-tyrosinase activity.

The human skin is constantly exposed to external factors that affect its integrity, UV radiation being one of the main stress factors. The repeated exposure to this radiation leads to increased production of Reactive Oxygen Species (ROS) which activate a series of processes involved in photoaging. Excessive UV exposure also exacerbates melanin production leading to a variety of pigmentation disorders. Xanthones are reported to exhibit properties that prevent deleterious effects of UV exposure and high levels of ROS in the organism, so in this work a wide library of xanthones with different patterns of substitution was synthesized and tested for their inhibitory activity against the skin enzymes tyrosinase, elastase, collagenase and hyaluronidase, many of which were evaluated for the first time. Most of the compounds were tyrosinase inhibitors, with the best one (xanthone 27) presenting an IC50 of 1.9 µM, which is approximately 6 times lower than the IC50 of the positive control kojic acid. Concerning the other enzymes, only one compound presented IC50 lower than 150 µM in elastase inhibition (xanthone 14 = 91.8 µM) and none in collagenase and hyaluronidase inhibition. A QSAR model for tyrosinase inhibitory activity was built using six molecular descriptors, with a partial negative surface area descriptor and the relative number of oxygen atoms being positively contributing to the tyrosinase inhibitory activity. Docking using AutoDock Vina shows that all the tested compounds have more affinity to mushroom tyrosinase than kojic acid. Docking results implied that the tyrosinase inhibitory mechanisms of xanthonic derivatives are attributed to an allosteric interaction. Taken together, these data suggest that xanthones might be useful scaffolds for the development of new and promising candidates for the treatment of pigmentation-related disorders and for skin whitening cosmetic products.

Alginate microparticles as carriers for the UV filter 2-ethylhexyl 4-methoxycinnamate: Influence on photostability.

OBJECTIVE: The organic ultraviolet UVB filter 2-ethylhexyl 4-methoxycinnamate (EHMC) was encapsulated in microparticles (MPs) of sodium alginate and co-loaded with vitamin E (Vit.E) by an extrusion process using an aerodynamically assisted jetting (AAJ) methodology. The aim was to assess the effect of encapsulation concerning UVB filter release from the MPs and its photochemical stability. METHODS: The EHMC photostability was analysed by exposing the samples (both MPs in aqueous dispersion and incorporated in a cream preparation) during 1 h to simulated solar light. For the MPs (empty-MP, EHMC-MP and EHMC + Vit.E-MP), the morphology and size were characterized; while in the case of the encapsulated samples, the amount of EHMC-loading was determined. The release of EHMC was evaluated by adding EHMC-MP or EHMC + Vit.E-MP to 65% ethanol in water under mechanical stirring at 32°C. RESULTS: All MPs showed a homogeneous size distribution with a median of 90.5 ± 2.5 µm for EHMC-MP and 70.4 ± 1.14 µm for EHMC + Vit.E-MP. The encapsulation efficiency was 92.9% and 99.4% for EHMC-MP and EHMC + Vit.E-MP, respectively. The observed release from the MPs was lower than the dissolution of the pure UV filter. EHMC-MP and EHMC + Vit.E-MP were successfully incorporated into a cream formulation, with no evidence of phase separation or colour modification. Upon simulated light exposure, the photoisomerization/phototransformation of EHMC encapsulated in MPs and Vit.E-MP decreased as compared to free EHMC, both in aqueous dispersion and as a cream. The conformational ratio of the isomers (Z-/E-EHMC) was found to be the lowest in the presence of Vit.E. CONCLUSION: This work demonstrates that use of these alginate microparticulate carriers could enhance the effectiveness of sunscreen preparations containing this UVB filter.

OBJECTIF: Le filtre ultraviolet organique D'UVB 2-éthylhexyl 4-methoxycinnamate (EHMC) a été encapsulé dans des microparticules (MPs) d'alginate de sodium et co-chargé avec la vitamine E (Vit.E) par un processus d'extrusion utilisant une méthode de jet assisté aérodynamique (AAJ). L'objectif était d'évaluer l'effet de l'encapsulation concernant la libération du filtre UVB par les MPs et sa stabilité photochimique. MÉTHODES: La photostabilité EHMC a été analysée en exposant les échantillons (les deux MPs en dispersion aqueuse et incorporés dans une préparation de type crème) pendant 1 h à la lumière solaire simulée. Pour les MPs (MP-vide, EHMC-MP et EHMC - Vit.E-MP), la morphologie et la taille ont été caractérisées; tandis que dans le cas des échantillons encapsulés, la quantité de charge EHMC a été déterminée. Le relargage de l'EHMC a été évalué en ajoutant EHMC-MP ou EHMC - Vit.E-MP à 65% d'éthanol dans l'eau sous agitation mécanique à 32°C. RÉSULTATS: Tous les MP ont montré une distribution homogène de taille avec une médiane de 90,5 +- 2,5 µm pour EHMC-MP et de 70,4 +- 1,14 µm pour l'EHMC et Vit.E-MP. L'efficacité de l'encapsulation était de 92,9 % et 99,4 % pour EHMC-MP et EHMC - Vit.E-MP, respectivement. Le relargage observé des MPs était inférieur à la dissolution du filtre UV pur. EHMC-MP et EHMC - Vit.E-MP ont été incorporés avec succès dans une formulation de crème, sans aucune preuve de séparation de phase ou de modification des couleurs. Après exposition à la lumière simulée, la photoiomérisation/phototransformation de l'EHMC encapsulée dans les MPs et Vit.E-MP a diminué par rapport à l'EHMC libre, à la fois dans la dispersion aqueuse et la crème. Le rapport conformationnel des isomères (Z-/E-EHMC) s'est avéré le plus bas en présence de Vit.E.

Implementation of an in vitro methodology for phototoxicity evaluation in a human keratinocyte cell line.

To assess photoxicity, several in vitro methods using different cellular models have been developed for preclinical testing. Over prediction of the in vivo photosafety hazard has been however appointed. Herein, we describe the implementation and validation of an in vitro methodology for phototoxicity evaluation based on the 3T3 neutral red uptake phototoxicity test using the HaCaT human keratinocyte cell line, and UVA/UVB radiation. Known positive (5-methoxypsoralen, chlorpromazine, and quinine) and negative (acetyl salicylic acid, hexachlorophene, and sodium lauryl sulphate) controls were tested together with a set of chemical currently used in cosmetic/pharmaceutical formulations. Apart from the advantage of using a cell line of human origin, these cells were generally more resistant to the cytotoxic effects of the test substances relative to the 3T3 mouse fibroblasts when exposed to an UVA irradiation dose of 1.7 mW/cm2. Therefore, this HaCaT NRU assay provides a more realistic experimental model that overcomes the over/high sensitivity frequently noted with the 3T3 NRU assay and that is more consistent with the human in vivo situation. Using a more representative method can prevent time-consuming and expensive in vivo testing in both animal models and humans that can significantly delay the clinical development of new chemicals.

Evolution of the use of antioxidants in anti-ageing cosmetics.

OBJECTIVE: Skin health and beauty are a cornerstone of general well-being in humans. Anti-ageing cosmetics are used to provide a healthy and youthful appearance. Among the different cosmetic actives, antioxidants are incorporated in anti-ageing products due to their beneficial effects in preventing and minimizing the signs of skin ageing. This work aims to understand how anti-ageing formulations changed in the past 7 years regarding pure antioxidants composition. METHODS: Data were collected from anti-ageing formulations commercialized in main stores and pharmacies in the Portuguese market. The study started on 2011 and was updated with products launched or whose composition has been renewed on 2013, 2015 or 2018. RESULTS: Ascorbic acid and tocopherol and their derivatives were consistently the most used antioxidants in anti-ageing formulations; followed by niacinamide and retinyl palmitate. Seven ascorbic acid derivatives are currently used in anti-ageing formulations while only three tocopherol derivatives were identified in this study. Several combinations of antioxidants were routinely found, mainly tocopherol (or tocopherol derivatives) with other antioxidants and tocopherol with tocopherol derivatives. We have not identified emerging antioxidants with great impact in anti-ageing formulations even though niacinamide and retinyl palmitate exhibited over 10% more usage in 2018. CONCLUSION: This insight is relevant to the cosmetic industry providing a better understanding of the scientific-based formulation of modern cosmetics and supports the need for innovative antioxidants in anti-ageing cosmetics.

OBJECTIF: La santé de la peau et la beauté constituent la base du bien-être général chez l'homme. Les cosmétiques anti-âge sont utilisés pour donner une apparence saine et jeune. Parmi les différents principes actifs des cosmétiques, des antioxydants sont incorporées dans les produits anti-âge en raison de leur effet bénéfique sur la prévention et la réduction des signes de vieillissement de la peau. Ce travail vise à comprendre comment les formulations anti-âge ont évolué au cours des 7 dernières années au niveau des antioxydants purs composition. MÉTHODES: Les données ont été recueillies sur des formulations anti-âge commercialisées dans les principaux magasins et pharmacies du marché portugais. Cette étude a commencé en 2011 et a été mise à jour avec des produits mis sur le marché ou dont la composition a été renouvelée en 2013, 2015 ou 2018. RÉSULTATS: L'acide ascorbique et tocophérol et leurs dérivés sont systématiquement les antioxydants les plus utilisés dans les formulations anti-âge; ils sont suivis de la niacinamide et du palmitate de rétinol. Sept dérivés d'acide ascorbique sont actuellement utilisés pour lutter contre le vieillissement, tandis que seulement trois dérivés de tocophérol ont été identifiés dans cette étude. Plusieurs combinaisons d'antioxydants ont été systématiquement observées, principalement le tocophérol ou les dérivés de tocophérol avec d'autres antioxydants, et le tocophérol avec des dérivés de tocophérol. Nous n'avons pas identifié de nouveaux antioxydants présentant un impact majeur dans les formulations anti-âge, même si la niacinamide et le palmitate de rétinol ont vu leur utilisation augmenter de 10% en 2018. CONCLUSION: Cette perspective est pertinente pour le secteur des cosmétiques. Elle permet de mieux comprendre la formulation scientifique des cosmétiques modernes et confirme le besoin d'innover au niveau des antioxydants utilisés dans les produits anti-âge. Les cosmétiques anti-âge sont utilisés pour donner une apparence saine et jeune. Parmi les différents actifs cosmétiques, les antioxydants sont incorporés dans les produits anti-âge en raison de leurs effets bénéfiques dans la prévention et la réduction des signes du vieillissement cutané. Ce travail vise à comprendre comment les formulations anti - vieillissement ont changé au cours des 7 dernières années en ce qui concerne la composition en antioxydants purs.

Mechanical Properties of Topical Anti-Psoriatic Medicines: Implications for Patient Satisfaction with Treatment.

Different types of topical preparations are available as anti-psoriatic medicines, semisolid formulations being the preferred dosage forms for the treatment of body lesions. The mechanical characterization of these semisolid formulations is seldom reported, although mechanical features have been recognized to play an important role in treatment acceptability and adherence. The aim of this study was to characterize the mechanical properties of semisolid topical formulations commercially available for psoriasis treatment. One complementary aim was to evaluate patient satisfaction with topical treatment and discuss the results according to the mechanical features of the dosage form. Eight ointments (O 1-8), five creams (C 1-5), one oleogel (G1), and one excipient (E1-petrolatum) were characterized for textural properties (spreadability and penetration tests) and flow behavior. Power law model was fitted to the results. A questionnaire for the assessment of satisfaction with topical medicines used for psoriasis treatment over 6 months was developed and applied to 79 psoriasis patients. All the tested formulations presented a shear-thinning behavior with power law indexes (n) lower than 1. Ointments were distinct from the other dosage forms, since they presented higher consistency coefficients (K), firmness, and adhesiveness and this was evidenced by hierarchical cluster analysis, which identified two clusters based on the mechanical properties. Cluster 1 included the ointments and petrolatum and the cluster 2 enclosed the creams and the gel. The clusters were associated with several attributes classified by patients as analyzed with Fisher's exact test. In all cases, higher satisfaction was observed for cluster 2. The knowledge obtained regarding the influence of the dosage form on the degree of satisfaction with the treatment could be helpful in supporting the selection of the dosage form in clinical practice and thus improve treatment adherence and clinical outcomes. The differences observed between the mechanical properties of the formulations studied may be also relevant to the industry, as guidance to the development of new medicines.

Patient preferences for attributes of topical anti-psoriatic medicines.

Background: Patient preferences should be considered when prescribing topical treatments to drive up adherence and improve clinical outcomes. Objective: The aim of this work was to identify the most important attributes of topical medicines for psoriasis treatment in the patients' view, and explore the sociodemographic and clinical determinants of these preferences. Methods: A questionnaire for the evaluation of the relevancy given to specific attributes of topical medicines used for psoriasis treatment was developed (PSO-TOPAP) and was applied to a total of seventy-nine patients, members of the Portuguese Association of Psoriasis (PSOPortugal) or outpatients of a dermatology unit of a central hospital. Results: Overall, attributes belonging to the formulation and application domains were greatly valued over attributes related to the container. Only a small number of patient preferences was influenced by age, gender, duration of the disease and age at first diagnosis. Limitations: Our findings need to be verified in larger and more diverse patient samples before generalization can be made. Conclusion: The insight obtained in this work can provide guidance to pharmaceutical drug product design and has also the potential to improve patient care through the acknowledgment of patient preferences in clinical practice.

Photostabilization strategies of photosensitive drugs.

PURPOSE: Several active compounds are sensitive to light, especially to the ultraviolet radiation (UV-R) leading to their degradation or modification, with lost or decrease of their biological activity. The aim of this study was to perform a systematic review regarding photostabilization strategies used on health products and perform a critical appraisal of their effectiveness. RESULTS: The bibliographic search identified 2261 results and merely 40 studies met the selection criteria. Of these, 85% referred to encapsulation strategies, 10% to antioxidants and 5% to the use of solar filters. Cyclodextrins (CD's) were the most used encapsulation systems (32.5%) followed by liposomes and lipid nanoparticles (each 17.5%), microparticles (15%) and polymeric nanoparticles (10%). The most effective were found to be liposomes and lipid nanoparticles. However, the different methodological conditions used limit the true relevance of this finding. CONCLUSIONS: A gold standard strategy suitable for all compounds cannot be proposed. Instead, case-by-case evaluation, supported on the photodegradation mechanism is recommended. Systematic studies that compare different photostabilization strategies undertaken with the same irradiation conditions are also needed.

In vitro cytotoxicity evaluation of resveratrol-loaded nanoparticles: Focus on the challenges of in vitro methodologies.

Assessment of toxic effects is mandatory before market placement of pharmaceutical and cosmetic products. Nanotoxicology is an emerging regulatory concern and still a challenging field. Topical application of resveratrol (RSV) has been extensively studied owing to its multi-mechanistic skin anti-aging effects. Nanoencapsulation has been suggested as a promising solution to overcome RSV stability issues. In this work RSV-loaded solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were prepared using a homogenization/sonication technique. Cytotoxicity assays were conducted with an immortalized cell line of human keratinocytes (HaCaT). For a comprehensive cytotoxicity characterization MTT and Alamar Blue® reduction assays (assessment of metabolic activity), Neutral red uptake (evaluation of lysosomal integrity), and Trypan blue (assessment of membrane integrity) were used. The results obtained with the different assays were not always concordant, as put in evidence by an adequate statistical analysis. Experimental parameters such as washing steps were found to be critical. The study is of interest because it draws attention to the importance of careful selected experimental conditions of in vitro nanotoxicological tests. Experimental protocols should be adapted taking into account nano-related features such as interference with the dyes and light dispersion/absorption properties.

Protective effect of C. sativa leaf extract against UV mediated-DNA damage in a human keratinocyte cell line.

Toxic effects of ultraviolet (UV) radiation on skin include protein and lipid oxidation, and DNA damage. The latter is known to play a major role in photocarcinogenesis and photoaging. Many plant extracts and natural compounds are emerging as photoprotective agents. Castanea sativa leaf extract is able to scavenge several reactive species that have been associated to UV-induced oxidative stress. The aim of this work was to analyze the protective effect of C. sativa extract (ECS) at different concentrations (0.001, 0.01, 0.05 and 0.1 µg/mL) against the UV mediated-DNA damage in a human keratinocyte cell line (HaCaT). For this purpose, the cytokinesis-block micronucleus assay was used. Elucidation of the protective mechanism was undertaken regarding UV absorption, influence on (1)O2 mediated effects or NRF2 activation. ECS presented a concentration-dependent protective effect against UV-mediated DNA damage in HaCaT cells. The maximum protection afforded (66.4%) was achieved with the concentration of 0.1 µg/mL. This effect was found to be related to a direct antioxidant effect (involving (1)O2) rather than activation of the endogenous antioxidant response coordinated by NRF2. Electrochemical studies showed that the good antioxidant capacity of the ECS can be ascribed to the presence of a pool of different phenolic antioxidants. No genotoxic or phototoxic effects were observed after incubation of HaCaT cells with ECS (up to 0.1 µg/mL). Taken together these results reinforce the putative application of this plant extract in the prevention/minimization of UV deleterious effects on skin.

Photodegradation of avobenzone: stabilization effect of antioxidants.

Avobenzone is one of the most common UVA-filters in sunscreens, and is known to be photounstable. Some of the strategies used to stabilize this filter present some drawbacks like photosensitization reactions. Antioxidants are widely used as cosmetic ingredients that prevent photoageing and complement the photoprotection offered by the UV-filters preventing or reducing photogenerated reactive species. The purpose of this work was to study the effect of antioxidants in the photostabilization of avobenzone. The filter dissolved in dimethyl sulfoxide or incorporated in a sunscreen formulation was irradiated with simulated solar radiation (750 W/m(2)). The tested antioxidants were vitamin C, vitamin E, and ubiquinone. The area under the curve of the absorption spectrum for UVA range and the sun protection factor (SPF) were calculated. Vitamin E (1:2), vitamin C (1:0.5) and ubiquinone (1:0.5) were the more effective concentrations increasing the photostability of avobenzone. In sunscreen formulations, the most effective photostabilizer was ubiquinone which also promoted an increase in SPF. This knowledge is important to improve effectiveness of sunscreen formulation. Antioxidants can be valuable ingredients for sunscreens with a triple activity of filter stabilization, SPF boosting and photoageing prevention.

Bacterial cellulose membranes as drug delivery systems: an in vivo skin compatibility study.

Bacterial cellulose (BC) is a highly pure form of cellulose, produced in the form of a swollen membrane by several bacteria that demonstrated to be able to modulate the skin release of model drugs. In the present study, the skin irritation potential of BC was evaluated in human subjects. BC membranes with and without glycerin (acting as plasticizer) were tested. No significant differences were observed for transepidermal water loss (TEWL) measurements in comparison with negative control, 2 and 24 h after patch removal, which is an indicator of an absence of barrier disruption. Similar results were found for erythema. Clinical scores were zero at both times for all volunteers, with the exception of five volunteers that exhibited weak reactions. BC with glycerin provided a skin moisturizing effect statistically higher than the negative control (p=0.044), which was not observed for BC alone. The good skin tolerance found after a single application under occlusion reinforces the putative interest of BC membranes as supports for drug topical delivery. Besides modifying the mechanical properties, the inclusion of glycerin results in a skin moisturizing effect which could be clinically relevant for the treatment for skin diseases characterized by dryness, such as psoriasis and atopic dermatitis.

Moisturizing effect of oleogel/hydrogel mixtures.

The aim of this study was to obtain new vehicles for topical formulations based on the mixture of hydrogels (aqueous systems) with oleogels (lipophilic systems). Several formulations were prepared using different oleogels mixed with polyacrylic acid hydrogel without addition of other ingredients. The moisturizing effect of the bigels was assessed along with the hydrogel and oleogels used in their preparation by carrying out an in vivo study with 14 healthy volunteers. Corneometer measurements were taken each hour during a five-hour period after product's application. Stability tests (storage at 20 and 40 degrees C for six months) and mechanical characterization were also carried out. Stability tests showed no modifications of the textural properties and appearance over a six-month period at 20 degrees C. At accelerated conditions, modifications of colour and textural properties were detected after six months' storage. While retaining the mechanical and sensory properties of the hydrogel, the bigels showed simultaneously an enhanced moisturizing effect, making them promising candidates for topical formulations.