Photopatch testing: Clinical characteristics, test results, and final diagnoses from the North American Contact Dermatitis Group, 2009-2020.

BACKGROUND: Photoallergic contact dermatitis (PACD) is a delayed hypersensitivity reaction to allergens only in the presence of ultraviolet radiation in sunlight. Photopatch testing (PhotoPT) is necessary to confirm the diagnosis of PACD. There are few published studies of PhotoPT in North America. OBJECTIVE: To summarise the results of patients photopatch tested by members of the North American Contact Dermatitis Group (NACDG), 2009-2020. METHODS: Retrospective analysis of patient characteristics and PhotoPT results to 32 allergens on the NACDG Photopatch Test Series. RESULTS: Most of the 454 tested patients were female (70.3%), 21-60 years old (66.7%) and White (66.7%). There were a total of 119 positive photopatch tests. Sunscreen agents comprised 88.2% of those, with benzophenones responsible for over half of them. Final diagnoses included PACD in 17.2%, allergic contact dermatitis (ACD) in 44.5%, polymorphous light eruption (PMLE) in 18.9% and chronic actinic dermatitis (CAD) in 9.0% of patients. CONCLUSIONS: In 454 patients with suspected photosensitivity referred for photopatch testing in North America, approximately one-fifth had PACD. Sunscreen agents, especially benzophenones, were the most common photoallergens. Other common diagnoses included ACD, PMLE and CAD. Photopatch testing is an important tool for differentiating these conditions.

Sunscreen use during recreational activities on a French Atlantic beach: release of UV filters at sea and influence of air temperature.

Organic UV filters are emerging contaminants in personal care products such as sunscreens. The toxicity of numerous of these UV filter compounds has been demonstrated in several marine taxa. However, whilst the biological impact has already been largely demonstrated, the anthropogenic drivers leading to UV filter contamination still need to be identified. In this work, a survey was conducted on a site of the French Atlantic Coast (i) to describe beachgoers' behaviours (sunscreen use and beach frequentation), (ii) provide an estimation of the UV filters released at sea and (iii) highlight the effect of air temperature on these behaviours and on the release of UV filters. In parallel with these estimations of the UV filters released at sea, in situ chemical measurements were performed. By comparing the results of both approaches, this interdisciplinary work provides an insight of how the observations of beachgoers' behaviour modulations and attendance level fluctuations could be used to prevent UV filter contaminations and ultimately manage the ecotoxicological risk.

Sunscreens Part 2: Regulation and Safety.

The second part of this CME article discusses sunscreen regulation and safety considerations for humans and the environment. First, we provide an overview of the history of the United States Food and Drug Administration's regulation of sunscreen. Recent Food and Drug Administration studies clearly demonstrate that organic ultraviolet filters are systemically absorbed during routine sunscreen use, but to date there is no evidence of associated negative health effects. We also review the current evidence of sunscreen's association with vitamin D levels and frontal fibrosing alopecia, and recent concerns regarding benzene contamination. Finally, we review the possible environmental effects of ultraviolet filters, particularly coral bleaching. While climate change has been shown to be the primary driver of coral bleaching, laboratory-based studies suggest that organic ultraviolet filters represent an additional contributing factor, which led several localities to ban certain organic filters.

Combined effects of organic and mineral UV-filters on the lugworm Arenicola marina.

Pollution from personal care products, such as UV-filters like avobenzone and nano-zinc oxide (nZnO), poses a growing threat to marine ecosystems. To better understand this hazard, especially for lesser-studied sediment-dwelling marine organisms, we investigated the physiological impacts of simultaneous exposure to nZnO and avobenzone on the lugworm Arenicola marina. Lugworms were exposed to nZnO, avobenzone, or their combination for three weeks. We assessed pollutant-induced metabolic changes by measuring key metabolic intermediates in the body wall and coelomic fluid, and oxidative stress by analyzing antioxidant levels and oxidative lesions in proteins and lipids of the body wall. Exposure to UV filters resulted in shifts in the concentrations of Krebs' cycle and urea cycle intermediates, as well as alterations in certain amino acids in the body wall and coelomic fluid of the lugworms. Pathway enrichment analyses revealed that nZnO induced more pronounced metabolic shifts compared to avobenzone or their combination. Exposure to avobenzone or nZnO alone prompted an increase in tissue antioxidant capacity, indicating a compensatory response to restore redox balance, which effectively prevented oxidative damage to proteins or lipids. However, co-exposure to nZnO and avobenzone suppressed superoxide dismutase and lead to accumulation of lipid peroxides and methionine sulfoxide, indicating oxidative stress and damage to lipids and proteins. Our findings highlight oxidative stress as a significant mechanism of toxicity for both nZnO and avobenzone, especially when combined, and underscores the importance of further investigating the fitness implications of oxidative stress induced by these common UV filters in benthic marine organisms.

Evaluation of the photoprotective and antioxidant potential of an avobenzone derivative.

Solar radiation can cause damage to the skin, and the use of sunscreens is one of the main protective measures. However, photounstable ultraviolet (UV) filters can generate photoproducts and reactive oxygen species (ROS). Adding antioxidants, such as resveratrol, to enhance the action of UV filters in sunscreens is an interesting strategy for reducing the damage caused by UV radiation exposure. However, new compounds must have their stability, safety and efficacy guaranteed. Avobenzone, a commonly used UV filter, stands out as a promising candidate for structural modification to enhance its stability. Its molecular hybridization with other UV filters and antioxidants can lead to safer and more effective compounds. In this study, the photoprotective and antioxidant potential of a derivative of avobenzone, hybridized with resveratrol's molecule, was evaluated using in vitro models of cells in monolayer and reconstructed human skin (RHS). Phototoxic potential was assessed using fibroblasts, while the antioxidant activity was measured using the DCFH2-DA probe in HaCaT keratinocytes and in-house RHS. The derivative exhibited UV absorption and demonstrated photostability. It did not exhibit any phototoxic nor photoreactivity potential. Additionally, it was able to photo stabilize a combination of photounstable UV filters, avobenzone and octyl methoxycinnamate, and to reduce their phototoxic potential. In terms of antioxidant activity, the derivative successfully protected against UVA-induced ROS production in the HaCaT keratinocytes model, showing statistical equivalence to the antioxidant control, quercetin (10 µg/mL). Furthermore, experiments conducted in the RHS model demonstrated a significant reduction of 30.7% in ROS generation compared to the irradiated control. This study demonstrated that structural modifications of avobenzone can lead to the development of a broad spectrum (absorbing UVB and UVA II radiation, as well as a portion of the UVA I radiation), non-phototoxic, non-photoreactive and photostable derivative for sunscreen and anti-aging formulations. This derivative enhances protection against oxidative stress induced by UV radiation and improves the effectiveness of sun protection. In addition to the monolayer model, the use of a standardized in-house RHS model was highly relevant for evaluating the effects of UV radiation and skin aging. This model closely mimics human physiological conditions and enables the testing of new compounds and the investigation of protective mechanisms against skin damage.

Adverse Effects of Avobenzone on Boar Sperm Function: Disruption of Protein Kinase A Activity and Tyrosine Phosphorylation.

Avobenzone (AVO), an ultraviolet (UV) filter, is frequently used as an ingredient in personal cosmetics. This UV filter has been found to be easily exposed in swimming pools and beaches, and it has been detected in human urine and blood. Moreover, numerous studies have demonstrated that AVO exhibits endocrine-disrupting properties. Nevertheless, the effects of AVO on male fertility have not yet fully understood. Therefore, this study aimed to assess the effects of AVO on various sperm functions during capacitation. First, boar spermatozoa were treated with various AVO concentrations. After treatment, sperm motility and kinetic characteristics, capacitation status, intracellular adenosine triphosphate (ATP) levels, and sperm viability were evaluated. Moreover, Western blot analysis w.as conducted to evaluate protein kinase A (PKA) activity and tyrosine phosphorylation. As a result, AVO treatment significantly decreased total motility, progressive motility, and several kinetic characteristics at high concentrations (50 and 100 µM). Furthermore, the capacitation status dose-dependently decreased. Conversely, no significant differences in acrosome reaction, cell viability, and intracellular ATP levels were observed. However, the intracellular ATP level tended to decrease. In addition, AVO dose-dependently induced abnormal changes in PKA activity and tyrosine phosphorylation. Although AVO did not directly exert a toxic effect on cell viability, it ultimately negatively affected sperm functions through abnormal alterations in PKA activity and tyrosine phosphorylation. Thus, the potential implications on male fertility must be considered when contemplating the safe utilization of AVO.

Single and mixture toxicity evaluation of avobenzone and homosalate to male zebrafish and H295R cells.

Avobenzone and homosalate are widely used in sunscreens to provide ultraviolet (UV) protection, either as single compounds or in combination. Some UV filters exhibit estrogenic or anti-androgenic activities, however, studies regarding their interactions and toxicity in mixtures are limited. In this study, the effect of the toxicity of a binary mixture comprising avobenzone (0.72 µg L-1) and homosalate (1.02 and 103 µg L-1) on steroid hormone biosynthesis were investigated using male zebrafish and human adrenocortical carcinoma (H295R) cells. In fish exposed to homosalate, a significant decrease in the gonadosomatic index, testosterone level, and transcription of several genes (e.g, hsd3b2, cyp17a1, and hsd17b1) and a significant increase in the hepatosomatic index, liver steatosis, 17ß-estradiol level, and transcription of vtg gene were observed. These results suggest that estrogenic and anti-androgenic effects of homosalate were mediated by the steroidogenic pathway. The presence of 0.72 µg L-1 of avobenzone augmented the anti-androgenic responses in male fish. The testosterone level in the H295R cells were significantly decreased after they were exposed to homosalate alone or in combination with avobenzone, which is consistent with observations in male zebrafish. Further studies need to be conducted to understand the endocrine disrupting properties of long-term exposure to substances typically used in sunscreens.

Salting-out assisted liquid-liquid extraction combined with LC-MS/MS for the simultaneous determination of seven organic UV filters in environmental water samples: method development and application.

Organic UV filters (OUVFs), the active ingredient in sunscreens, are of environmental concern due to reported ecotoxicological effects in aquatic biota. Determining the environmental concentrations of these chemicals is essential for understanding their fate and potential environmental risk. Salting-out assisted liquid-liquid extraction (SALLE) coupled with liquid-chromatography tandem mass spectrometry (LC-MS/MS) was developed for simultaneous extraction, separation, and quantification of seven OUVFs (2,4-dihydroxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone, 4-methylbenzylidene camphor, butyl-methoxy-dibenzoyl methane, octocrylene, octyl methoxycinnamate, and oxybenzone). Method detection limits (MDLs) ranged from 11 to 45 ng/L and practical quantification limits (PQLs) from 33 to 135 ng/L. Method trueness, evaluated in terms of recovery, was 69-127%. Inter-day and intra-day variability was < 6% RSD. The coefficients of determination were > 0.97. The method was applied to river and seawater samples collected at 19 sites in and near Port Phillip Bay, Australia, and temporal variation in OUVF concentrations was studied at two sites. Concentrations of OUVF were detected at 10 sites; concentrations of individual OUVFs were 51-7968 ng/L, and the maximum total OUVF concentration detected at a site was 8431 ng/L. Recreational activity and water residence time at the site contributed to OUVF's environmental presence and persistence. The benefits of the SALLE-LC-MS/MS method include its simple operation, good selectivity, precision over a wide linear range, and that obtained extracts can be directly injected into the LC-MS/MS, overall making it an attractive method for the determination of these OUVFs in environmental water matrices. To our knowledge, this is the first report of the occurrence of OUVFs in Port Phillip Bay, Australia.

Characteristic Photoprotective Molecules from the Sphagnum World: A Solution-Phase Ultrafast Study of Sphagnic Acid.

A natural UV-absorbing chromophore extracted from sphagnum mosses, sphagnic acid, is proposed as a new natural support to chemical UV filters for use in cosmetic applications. Sphagnic acid is structurally related to the cinnamate family of molecules, known for their strong UV absorption, efficient non-radiative decay, and antioxidant properties. In this study, transient electronic absorption spectroscopy is used, in conjunction with steady-state techniques, to model the photodynamics following photoexcitation of sphagnic acid in different solvent systems. Sphagnic acid was found in each system to relax with lifetimes of ~200 fs and ~1.5 ps before generating a cis-isomer photoproduct. This study helps to elucidate the photoprotective mechanism of a new potential natural support to sunscreens, from a unique plant source.

Repurposing sunscreen as an antibiotic: zinc-activated avobenzone inhibits methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major healthcare concern with associated healthcare costs reaching over ${\$}$1 billion in a single year in the USA. Antibiotic resistance in S. aureus is now observed against last line of defense antibiotics, such as vancomycin, linezolid, and daptomycin. Unfortunately, high throughput drug discovery approaches to identify new antibiotics effective against MRSA have not resulted in much tangible success over the last decades. Previously, we demonstrated the feasibility of an alternative drug discovery approach, the identification of metallo-antibiotics, compounds that gain antibacterial activity only after binding to a transition metal ion and as such are unlikely to be detected in standard drug screens. We now report that avobenzone, the primary active ingredient of most sunscreens, can be activated by zinc to become a potent antibacterial compound against MRSA. Zinc-activated avobenzone (AVB-Zn) potently inhibited a series of clinical MRSA isolates [minimal inhibitory concentration (MIC): 0.62-2.5 µM], without pre-existing resistance and activity without zinc (MIC: >10 µM). AVB-Zn was also active against clinical MRSA isolates that were resistant against the commonly used zinc-salt antibiotic bacitracin. We found AVB-Zn exerted no cytotoxicity on human cell lines and primary cells. Last, we demonstrate AVB-Zn can be deployed therapeutically as lotion preparations, which showed efficacy in a mouse wound model of MRSA infection. AVB-Zn thus demonstrates Zn-activated metallo-antibiotics are a promising avenue for future drug discovery.

On the Fate of Butyl Methoxydibenzoylmethane (Avobenzone) in Coral Tissue and Its Effect on Coral Metabolome.

The intensive use of sunscreen products has raised concerns regarding their environmental toxicity and the adverse impacts of ultraviolet (UV) filters on ecologically important coral communities. Prior metabolomic analyses on symbiotic coral Pocillopora damicornis exposed to the UV filter butyl methoxydibenzoylmethane (BM, avobenzone) revealed unidentified ions in the holobiont metabolome. In the present study, follow-up differential metabolomic analyses in BM-exposed P. damicornis detected 57 ions with significantly different relative concentrations in exposed corals. The results showed an accumulation of 17 BM derivatives produced through BM reduction and esterification. The major derivative identified C16:0-dihydroBM, which was synthesized and used as a standard to quantify BM derivatives in coral extracts. The results indicated that relative amounts of BM derivatives made up to 95% of the total BM (w/w) absorbed in coral tissue after 7 days of exposure. Among the remaining metabolites annotated, seven compounds significantly affected by BM exposure could be attributed to the coral dinoflagellate symbiont, indicating that BM exposure might impair the photosynthetic capacity of the holobiont. The present results suggest that the potential role of BM in coral bleaching in anthropogenic areas should be investigated and that BM derivatives should be considered in future assessments on the fate and effects of BM in the environment.

Drug Delivery Strategies for Avobenzone: A Case Study of Photostabilization.

Several developments and research methods are ongoing in drug technology and chemistry research to elicit effectiveness regarding the therapeutic activity of drugs along with photoprotection for their molecular integrity. The detrimental effect of UV light induces damaged cells and DNA, which leads to skin cancer and other phototoxic effects. The application of sunscreen shields to the skin is important, along with recommended UV filters. Avobenzone is widely used as a UVA filter for skin photoprotection in sunscreen formulations. However, keto-enol tautomerism propagates photodegradation into it, which further channelizes the phototoxic and photoirradiation effects, further limiting its use. Several approaches have been used to counter these issues, including encapsulation, antioxidants, photostabilizers, and quenchers. To seek the gold standard approach for photoprotection in photosensitive drugs, combinations of strategies have been implemented to identify effective and safe sunscreen agents. The stringent regulatory guidelines for sunscreen formulations, along with the availability of limited FDA-approved UV filters, have led many researchers to develop perfect photostabilization strategies for available photostable UV filters, such as avobenzone. From this perspective, the objective of the current review is to summarize the recent literature on drug delivery strategies implemented for the photostabilization of avobenzone that could be useful to frame industrially oriented potential strategies on a large scale to circumvent all possible photounstable issues of avobenzone.

TiO2-embedded mesoporous silica with lower porosity is beneficial to adsorb the pollutants and retard UV filter absorption: A possible application for outdoor skin protection.

The purpose of the current investigation was to develop multifunctional TiO2-embedded mesoporous silica incorporating avobenzone to protect against environmental stress through pollutant adsorption and UVA protection. We sought to explore the effect of the mesoporous porosity on the capability of contaminant capture and the suppression of avobenzone skin penetration. The porosity of the mesoporous silica was tuned by adjusting the ratio of template triblock copolymers (Pluronic P123 and F68). The Pluronic P123:F68 ratios of 3:1, 2:2, and 1:3 produced mesoporous silica with pore volumes of 0.66 (TiO2/SBA-L), 0.47 (TiO2/SBA-M), and 0.25 (TiO2/SBA-S) cm3/g, respectively. X-ray scattering and electron microscopy confirmed the SBA-15 structure of the as-prepared material had a size of 3-5 µm. The maximum adsorbability of fluoranthene and methylene blue was found to be 43% and 53% for the TiO2/SBA-S under UVA light, respectively. The avobenzone loaded into the mesoporous silica demonstrated the synergistic effect of in vitro UVA protection, reaching an UVA/UVB absorbance ratio of near 1.5 (Boots star rating = 5). The encapsulation of avobenzone into the TiO2/SBA-S lessened cutaneous avobenzone absorption from 0.76 to 0.50 nmol/mg, whereas no reduction was detected for the TiO2/SBA-L. The avobenzone-loaded TiO2/SBA-S hydrogel exhibited a greater improvement in skin barrier recovery and proinflammatory mediator mitigation compared to the SBA-S hydrogel (without TiO2). The cytokines/chemokines in the photoaged skin were reduced by two- to three-fold after TiO2/SBA-S treatment compared to the non-treatment control. Our data suggested that the mesoporous formulation with low porosity and a specific surface area showed effective adsorbability and UVA protection, with reduced UVA filter absorption. The versatility of the developed mesoporous system indicated a promising potential for outdoor skin protection.

Significance of D- tryptophan in Contryphan-Ar1131 Conus peptide: Oxidative folding, trypsin binding, and photostabilization activity.

Distinct differences have been observed between L-tryptophan and D-tryptophan containing contryphan-Ar1131 in oxidative folding, trypsin binding, and photostabilization activity on avobenzone. [W5] contryphan-Ar1131 and [w5] contryphan-Ar1131 were chemically synthesized and characterized using RP-HPLC and mass spectrometry. Structural differences due to the change of configuration of tryptophan were evident from the optimized structures of contryphan-Ar1131 using density functional theory (DFT). The comparison of early events of oxidative folding has revealed the role of D-tryptophan in accelerating the formation of a disulfide bond. The optimized structures of the reduced form of peptides revealed the occurrence of aromatic-aromatic and aromatic-proline interactions in [w5] contryphan-Ar1131 which may be critical in aiding the oxidative folding reaction. The presence of the Lys6-Pro7 peptide bond indicates that contryphan-Ar1131 is resistant but may bind to trypsin allowing to assign the binding affinity of peptides to the protein surface. Competitive binding studies and molecular docking along with molecular dynamic (MD) simulations have revealed that [w5] contryphan-Ar1131 has more affinity for the active site of trypsin. Given tryptophan is a photostabilizer of FDA-approved chemical UV-A filter avobenzone, the report has compared the photostabilization activity of [W5]/ [w5] contryphan-Ar1131 on avobenzone under natural sunlight. [w5] contryphan-Ar1131 has better photostabilization activity than that of [W5] contryphan-Ar1131 and also individual D-tryptophan and L-tryptophan amino acids. These biochemical studies have highlighted the significance of D-tryptophan in contryphan-Ar1131 and its photostabilization activity on avobenzone may find applications in cosmetics.

Waterborne exposure to avobenzone and octinoxate induces thyroid endocrine disruption in wild-type and thrαa-/- zebrafish larvae.

Avobenzone and octinoxate are frequently used as organic ultraviolet filters, and these chemicals are widely detected in water. This study evaluated the potential of avobenzone and octinoxate to disrupt thyroid endocrine system in wild-type and thyroid hormone receptor alpha a knockout (thrαa-/-) zebrafish embryo/larvae. Following a 120 h exposure to various concentrations of avobenzone and octinoxate, larvae mortality and developmental toxicity in wild-type and thrαa-/- fish were assessed. Triiodothyronine (T3) and thyroxine (T4) levels as well as transcriptional levels of ten genes associated with the hypothalamus-pituitary-thyroid (HPT) axis were measured in wild-type fish. Significantly lower larvae survival rate in thrαa-/- fish exposed to ≥3 µM avobenzone and octinoxate suggests that the thyroid hormone receptor plays a crucial role in the toxic effects of avobenzone and octinoxate. A significant increase in the deio2 gene level in avobenzone-exposed zebrafish supports the result of an increased ratio of T3 to T4. Significant decrease of T4 level with upregulation of trh, tshß, and tshr genes indicates feedback in the hypothalamus and pituitary gland to maintain hormonal homeostasis. Our observation indicates that exposure to avobenzone and octinoxate affects the thyroid hormone receptor and the feedback mechanisms of the HPT axis. CLINICAL TRIALS REGISTRATION: Not applicable.

Potential UV-Protective Effect of Freestanding Biodegradable Nanosheet-Based Sunscreen Preparations in XPA-Deficient Mice.

Xeroderma pigmentosum (XP) is a rare autosomal recessive hereditary disorder. As patients with XP are deficient in nucleotide excision repair, they show severe photosensitivity symptoms. Although skin protection from ultraviolet (UV) radiation is essential to improve the life expectancy of such patients, the optimal protective effect is not achieved even with sunscreen application, owing to the low usability of the preparations. Nanosheets are two-dimensional nanostructures with a thickness in the nanometer range. The extremely large aspect ratios of the nanosheets result in high transparency, flexibility, and adhesiveness. Moreover, their high moisture permeability enables their application to any area of the skin for a long time. We fabricated preparations containing avobenzone (BMDBM) based on freestanding poly (L-lactic acid) (PLLA) nanosheets through a spin-coating process. Although monolayered PLLA nanosheets did not contain enough BMDBM to protect against UV radiation, the layered nanosheets, consisting of five discrete BMDBM nanosheets, showed high UV absorbance without lowering the adhesive strength against skin. Inflammatory reactions in XPA-deficient mice after UV radiation were completely suppressed by the application of BMDBM-layered nanosheets to the skin. Thus, the BMDBM layered nanosheet could serve as a potential sunscreen preparation to improve the quality of life of patients with XP.

Methoxy-Monobenzoylmethane Protects Skin from UV-Induced Damages in a Randomized, Placebo Controlled, Double-Blinded Human In Vivo Study and Prevents Signs of Inflammation While Improving the Skin Barrier.

INTRODUCTION: Sun protection is important in skin care and requires special attention as inefficient protection might trigger skin pathologies including polymorphic light eruption (PLE). The reduce-improve-protect (RIP) concept to avoid the onset of ultraviolet (UV) irradiation-induced diseases or damage to human skin is important. Methoxy-monobenzoylmethane (MeO-MBM), which is neither a UVB nor a UVA filter, converts to the UV filter avobenzone under UV irradiation and further acts as a photoantioxidant during its conversion process and initially as an antioxidant material. The aim of this study was to understand the mechanisms by which MeO-MBM improves the condition of UV-stressed skin through its photoantioxidant properties. The improvement of the skin condition by the activity of MeO-MBM as active ingredient was also investigated. METHODS: Potential molecular targets were identified by in silico docking to numerous cellular membrane receptors on the cell surface or nuclear membrane, followed by microarray analysis of 164 genes after MeO-MBM treatment of normal human epidermal keratinocytes (NHEK). We conducted randomized, double-blinded, intra-individual comparison vs. placebo studies on ten volunteers, aged between 34 and 65 years, to assess the effect of MeO-MBM in vivo. The effect after UV-induced inflammation was assessed in a protective and curative set-up with 2% MeO-MBM vs. 1% hydrocortisone and placebo based on the change in blood flow. The barrier function of the skin was assessed by the change in transepidermal water loss (TEWL), skin scaling and skin thickness after the treatment with MeO-MBM. Additionally, the effect of MeO-MBM after UV-induced stress on the activation of ferritin in human explants was determined ex vivo. RESULTS: A docking simulation of MeO-MBM showed a potential interaction with the retinoic acid receptor gamma and further revealed downregulation of proteins related to inflammation. In the protective treatment set-up, after 24 h MeO-MBM significantly reduced the delta blood flow compared to placebo, while this reduction was more prominent with hydrocortisone. In the curative treatment set-up, a greater reduction in delta blood flow was also observed with MeO-MBM compared to placebo and similar to hydrocortisone. Treatment with MeO-MBM revealed an improvement in skin barrier function as a result of decreased TEWL, reduced skin scaling and increased skin thickness. Immunohistochemistry staining of ferritin on human skin explants further showed that the treatment with MeO-MBM reduced the ferritin expression. CONCLUSION: Based on these results, MeO-MBM is capable of exerting an anti-aging activity via the retinoic acid receptor gamma. Its anti-inflammatory and anti-oxidative activity manifested via the downregulation of multiple anti-inflammatory genes as well as the reduction of ferritin in skin tissue. This study shows that the multidimensional functionality of MeO-MBM offers an effective approach to combat acute and chronic deleterious effects of oxidative UV damage while simultaneously enhancing the skin barrier function.

Avobenzone and nanoplastics affect the development of zebrafish nervous system and retinal system and inhibit their locomotor behavior.

The use of cosmetics is growing with each passing day, arousing widespread attention to their ingredients. Avobenzone (AVO) and nanoplastics (NPs) are typical ingredients in cosmetics, which coexist in the aquatic environment and have a combined effect on aquatic organisms. In this study, the accumulation of AVO and NPs in zebrafish larvae and effects on gene expression and enzymatic activity related to nervous functions, and locomotor behavior were investigated. AVO and NPs accumulated continuously in zebrafish, and the combined exposure enhanced AVO accumulation. After recovery, the accumulated concentrations of AVO and NPs in zebrafish remained unchanged, suggesting that AVO and NPs could not be eliminated in 72 h. The genes regulated nervous system development were affected mainly by AVO exposure, while the genes regulated retinal system development were affected by NPs exposure. Single and combined exposures of AVO and NPs affected the activities of acetylcholinesterase and antioxidant enzymes in zebrafish, and superoxide dismutase activity could not return to normal level after 72 h of recovery period. The locomotor activity of zebrafish larvae was significantly inhibited by AVO and NPs, which might be related to the alterations in functions of nervous system development and retinal system development as well as the interference of neurotransmitter system and antioxidant system.

RP-HPLC simultaneous quantification of rutin, avobenzone, and octyl methoxycinnamate in the presence of hydroxypropyl β-cyclodextrin (HPβCD) and sulfobutyl ether β-cyclodextrin (SBEβCD)

Abstract Development and validation of a simple and fast method of high-performance liquid chromatography with diode array detection (HPLC-DAD) for the simultaneously analysis of rutin, avobenzone, and octyl p-methoxycinnamate is presented. These substances were separated using a Kromasil C18 (250×4.6 mm, 5 μm) column, methanol: water (88:12 v/v) as the mobile phase, and a flow rate of 0.8 mL min−1. The experiment was performed at room temperature and elution was under isocratic conditions. Quantification was performed by external calibration at the wavelength of 325 nm. The validated parameters included linearity, selectivity, precision (repeatability), intermediate precision, accuracy, limit of detection, limit of quantification and robustness. The results of validation were statistically treated using the Action Stat version 3.5.152.34. The selectivity was also evaluated in the presence of two cyclodextrins (2-hydroxypropyl-β-cyclodextrin and β-cyclodextrin sulfobutyl ether sodium). The absence of parallelism between the curves of octyl p-methoxycinnamate in the absence and presence of the β-cyclodextrin sulfobutyl ether sodium in the mobile phase revealed interference from this matrix, thereby indicating the necessity of validating the method in the presence of this, and other matrices. The proposed method was selective, linear, precise, accurate, and robust for the simultaneous determination of rutin, avobenzone, and octyl p-methoxycinnamate.

Preclinical and clinical studies to evaluate cutaneous biodistribution, safety and efficacy of UV filters encapsulated in mesoporous silica SBA-15.

Innovative technologies have been designed to improve efficacy and safety of chemical UV filters. Encapsulation can enhance efficacy and reduce transdermal permeation and systemic exposure. The aims of this work were (i) to determine the cutaneous biodistribution of avobenzone (AVO), oxybenzone (OXY), and octyl methoxycinnamate (OMC) incorporated in mesoporous silica SBA-15 and (ii) to perform preclinical (in vitro) and (iii) clinical safety studies to demonstrate their innocuity and to evaluate sun protection factor (SPF) in humans. Skin penetration studies showed that deposition of OXY and AVO in porcine and human skin after application of stick formulation with incorporated filters (stick incorporated filters) was significantly lower than from a marketed (non-encapsulated) stick. Cutaneous deposition and transdermal permeation of OXY in and across human skin were 3.8-and 13.4- fold lower, respectively, after application of stick entrapped filters. Biodistribution results showed that encapsulation in SBA-15 decreased AVO and OXY penetration reaching porcine and human dermis. Greater deposition (and permeation) of OXY in porcine skin than in human skin, pointed to the role of follicular transport. Stick incorporated filters had good biocompatibility in vivo and safety profiles, even under sun-exposed conditions. Entrapment of UV filters improved the SPF by 26% and produced the same SPF profile as a marketed stick. Overall, the results showed that SBA-15 enabled safety and efficacy of UV filters to be increased.