Applications of mycosporine-like amino acids beyond photoprotection.

Recent years have seen a lot of interest in mycosporine-like amino acids (MAAs) because of their alleged potential as a natural microbial sunscreen. Since chemical ultraviolet (UV) absorbers are unsafe for long-term usage, the demand for natural UV-absorbing substances has increased. In this situation, MAA is a strong contender for an eco-friendly UV protector. The capacity of MAAs to absorb light in the UV-A (320-400 nm) and UV-B (280-320 nm) range without generating free radicals is potentially relevant in photoprotection. The usage of MAAs for purposes other than photoprotection has now shifted in favor of medicinal applications. Aside from UV absorption, MAAs also have anti-oxidant, anti-inflammatory, wound-healing, anti-photoaging, cell proliferation stimulators, anti-cancer agents, and anti-adipogenic properties. Recently, MAAs application to combat SARS-CoV-2 infection was also investigated. In this review article, we highlight the biomedical applications of MAAs that go beyond photoprotection, which can help in utilizing the MAAs as promising bioactive compounds in both pharmaceutical and cosmetic applications.

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.

Genome Mining as an Alternative Way for Screening the Marine Organisms for Their Potential to Produce UV-Absorbing Mycosporine-like Amino Acid.

Mycosporine-like amino acids (MAAs) are small molecules with robust ultraviolet (UV)-absorbing capacities and a huge potential to be used as an environmentally friendly natural sunscreen. MAAs, temperature, and light-stable compounds demonstrate powerful photoprotective capacities and the ability to capture light in the UV-A and UV-B ranges without the production of damaging free radicals. The biotechnological uses of these secondary metabolites have been often limited by the small quantities restored from natural resources, variation in MAA expression profiles, and limited success in heterologous expression systems. Overcoming these obstacles requires a better understanding of MAA biosynthesis and its regulatory processes. MAAs are produced to a certain extent via a four-enzyme pathway, including genes encoding enzymes dehydroquinate synthase, enzyme O-methyltransferase, adenosine triphosphate grasp, and a nonribosomal peptide synthetase. However, there are substantial genetic discrepancies in the MAA genetic pathway in different species, suggesting further complexity of this pathway that is yet to be fully explored. In recent years, the application of genome-mining approaches allowed the identification of biosynthetic gene clusters (BGCs) that resulted in the discovery of many new compounds from unconventional sources. This review explores the use of novel genomics tools for linking BGCs and secondary metabolites based on the available omics data, including MAAs, and evaluates the potential of using novel genome-mining tools to reveal a cryptic potential for new bioproduct screening approaches and unrevealing new MAA producers.

A novel glyceroglycolipid from brown algae Ishige okamurae improve photoaging and counteract inflammation in UVB-induced HaCaT cells.

BACKGROUND: Excessive exposure to Ultraviolet (UV) rays can cause premature skin aging. Ishigoside (IGS) is a new glyceroglycolipid compound isolated from brown algal Ishige okamurae, However, whether it can protect the skin from (Ultraviolet-B) UVB damage has not been illuminated. METHODS: The in vitro anti-photoaging effect of IGS was conducted in UVB-induced HaCaT. The HaCaT cells were divided into the following five groups: (1) cells didn't suffer from UVB irradiation or IGS treatment. (2-5) Cells were treated with various concentrations of IGS (0, 10, 50, and 100 µM) and irradiated by 40 mJ/cm2 UVB. The Matrix metalloproteinase (MMP) of photoaging process was determined by ELISA kits and the latent interaction between IGS and MMP was further performed by molecular docking. The crucial signaling pathway proteins involved in the collagen synthesis and degradation were subsequently evaluated by Western blotting, immunofluorescence and EMSA. RESULTS: IGS effectively suppresses the high expressions and secretions of matrix metalloproteinases (MMPs) and photo-inflammation by blocking MAPKs, AP-1 and NF-κB. Meanwhile, increasing antioxidant enzyme expression. Molecular docking results suggest that inhibition of IGS on MMPs may be attributed to its hydrogen supply and hydrophobic capacity. In addition, IGS enhanced procollagen production by upregulating the TGF-ß/Smad pathways. CONCLUSIONS: IGS exhibited anti-photoaging activity in UVB-damage HaCaT. These effects might be a contribution by its suppression of MMPs expression via MAPKs, AP-1 and NF-κB pathway and have anti-oxidative and anti-inflammatory effects. Therefore, IGS has the great potential to become skin-care products or functional foods for preventing skin photoaging.

Benzophenone Accumulates over Time from the Degradation of Octocrylene in Commercial Sunscreen Products.

Benzophenone is a mutagen, carcinogen, and endocrine disruptor. Its presence in food products or food packaging is banned in the United States. Under California Proposition 65, there is no safe harbor for benzophenone in any personal care products, including sunscreens, anti-aging creams, and moisturizers. The purpose of this study was to determine (1) if benzophenone was present in a wide variety of commercial sun protection factor (SPF)/sunscreen products, (2) whether benzophenone concentration in the product increased over time, and (3) if the degradation of octocrylene was the likely source for benzophenone contamination. Benzophenone concentration was assayed in nine commercial sunscreen products from the European Union and eight from the United States (in triplicate), including two single ingredient sources of octocrylene. These same SPF items were subjected to the United States Food and Drug Administration (U.S. FDA)-accelerated stability aging protocol for 6 weeks. Benzophenone was measured in the accelerated-aged products. Sixteen octocrylene-containing product lines that were recently purchased had an average concentration of 39 mg/kg benzophenone, ranging from 6 mg/kg to 186 mg/kg. Benzophenone was not detectable in the product that did not contain octocrylene. After subjecting the 17 products to the U.S. FDA-accelerated stability method, the 16 octocrylene-containing products had an average concentration of 75 mg/kg, ranging from 9.8 mg/kg to 435 mg/kg. Benzophenone was not detectable in the product that did not contain octocrylene. Benzophenone was detected in the pure octocrylene manufactured ingredient. Octocrylene generates benzophenone through a retro-aldol condensation. In vivo, up to 70% of the benzophenone in these sunscreen products may be absorbed through the skin. U.S. FDA has established a zero tolerance for benzophenone as a food additive. In the United States, there were 2999 SPF products containing octocrylene in 2019. The safety of octocrylene as a benzophenone generator in SPF or any consumer products should be expeditiously reviewed by regulatory agencies.

Mycelial culture extracts of selected wood-decay mushrooms as a source of skin-protecting factors.

OBJECTIVES: This study analyzed the content of substances with cosmetologic properties in the extracts obtained from the mycelial cultures of Ganoderma applanatum, Laetiporus sulphureus, and Trametes versicolor. The effect of these extracts on the inhibition of tyrosinase and hyaluronidase was determined, and their values of sun protection factor (SPF) were calculated. RESULTS: The total amount of phenolic acids in the extracts ranged from 2.69 (G. applanatum) to 10.30 mg/100 g dry weight (T. versicolor). The total amount of sterols was estimated at 48.40 (T. versicolor) to 201.04 mg/100 g dry weight (L. sulphureus), and that of indoles at 2.90 (G. applanatum) to 16.74 mg/100 dry weight (L. sulphureus). Kojic acid was determined in the extracts of L. sulphureus and G. applanatum. It was observed that L. sulphureus extract caused dose-dependent inhibition of hyaluronidase, while all the extracts inhibited tyrosinase. The extract of G. applanatum exhibited an SPF value of ~ 9. CONCLUSIONS: The results showed that the mycelial cultures of the studied species may be used as an alternative source of substances used in cosmetology.

Characterization and photoprotective potentiality of lime dwelling Pseudomonas mediated melanin as sunscreen agent against UV-B radiations.

Prolonged exposure to Ultra Violet Radiation (UVR) adversely alters the functions of many skin cell types causing skin cancer and photoaging, which had led to increase in demand for more safe and natural sunscreens against UVR. The present study focuses on production, structural characterization and evaluation of photoprotective nature of melanin pigment derived from lime dwelling Pseudomonas sp. Melanin was characterized by solubility, UV-Vis, FT-IR, 13C-CPMAS, ESI-MS spectroscopy, including particle size, melting point and elemental analyses. In vitro cytotoxicity and photo-protective effect of Pseudomonas derived melanin (Mel-P) against UV-B (Broad Band-BB) radiations were assessed on mouse fibroblasts NIH 3 T3 cell lines. Reactive Oxygen Species (ROS) generated in NIH 3 T3 cells upon UV-B (BB) exposure was determined and quantified by Fluorescent microscopic and Flow cytometric analyses. A natural melanin obtained from Pseudomonas sp. contains 5,6- dihydroxy indole 2-carboxyic acid (DHICA) as its basic constituent and possess typical properties of eumelanin as revealed by the characterization studies. Mel-P has shown cell viability of 61.33 ± 6.58% at the concentration of 500 µg/mL proving its non-cytotoxic effect. Owing to its anti-oxidant property, melanin efficiently protected the mouse fibroblast cells from UV-B (BB) irradiation in a dose dependant manner demonstrating its potential as an active photoprotective agent.

Animal- free skin permeation analysis using mass spectrometry imaging.

Here we demonstrate an animal-free skin permeation analytical approach suitable for testing pharmaceuticals, cosmetics, occupational skin hazards and skin allergens. The method aims to replace or significantly reduce existing in-vivo models and improve on already established in-vitro models. This by offering a more sensitive and flexible analytical approach that can replace and/or complement existing methods in the OECD guidelines for skin adsorption (no 427 and no 428) and measure multiple compounds simultaneously in the skin while being able to also trace endogenous effects in cells. We demonstrate this here by studying how active ingredients in sunscreen permeate through left-over human skin, from routine surgery, in a in a Franz-cell permeation model. Two common sunscreens were therefore applied to the human skin and Time of flight secondary ion mass spectrometry (ToF-SIMS) was used to trace the molecules through the skin. We show that that ToF-SIMS imaging can be applied in visualizing the distribution of Avobenzone, Bemotrizinol, Biscotrizole and Ethyl hexyl triazine at subcellular resolution in the skin. The UV-blockers could be visualized at the same time in one single experiment without any probes or antibodies used. The UV-blockers mostly remained in the stratum corneum. However, in certain features of the skin, such as sebaceous glands, the penetration of the UV-blockers was more prominent, and the compounds reached deeper into the epidermis.

Streptomyces-Derived Metabolites with Potential Photoprotective Properties-A Systematic Literature Review and Meta-Analysis on the Reported Chemodiversity.

Sun overexposure is associated with the development of diseases that primarily affect the skin, which can lead to skin cancer. Among the main measures of photoprotection is the use of sunscreens. However, there is currently concern about the reported harmful effects to both humans and the environment due to several of the sunscreen ingredients available on the market. For this reason, the search for and development of new agents with photoprotective properties is required. In searching for these metabolites, researchers have turned their attention to microbial sources, especially the microbiota in unusual hostile environments. Among the diverse microorganisms available in nature, Actinobacteria and specifically Streptomyces, have been shown to be a source of metabolites with various biological activities of interest, such as antimicrobial, antitumor and immunomodulator activities. Herein, we present the results of a systematic review of the literature in which Streptomyces isolates were studied as a source of compounds with photoprotective properties. A meta-analysis of the structure-property and structure-activity relationships of those metabolites identified in the qualitative analysis phase was also carried out. These findings indicate that Streptomyces are a source of metabolites with potential applications in the development of new, safe and more eco-friendly sunscreens.

Synergistic effects of binary oil mixtures on the solubility of sunscreen UV absorbers.

Sunscreens for the photoprotection of human skin often are prepared as emulsions, containing organic UV-absorber molecules dissolved in the oil phase. The solubility of such oil-soluble UV-absorbers can be a limiting factor when aiming for high protection against UV-radiation. Possible synergistic effects of combinations of oil components toward UV-absorber solubility are therefore of great interest. Since a multitude of different combinations of oil components are possible, it would be desirable to predict synergistic effects by computational methods. As a model system, the solubility of a hydroxyphenyl triazine type UV-absorber was studied in several binary oil mixtures, experimentally and also by using a computational procedure based on density functional theory (DFT) and the continuum solvation model COSMO-RS. We have found good agreement of experimental and computational results. Computational methods may thus be employed to predict synergistic behaviour of solubility for systems containing two or more solvents.

Chemical Composition of a Novel Distillate from Fermented Mixture of Nine Anti-Inflammatory Herbs and Its UVB-Protective Efficacy in Mouse Dorsal Skin via Attenuating Collagen Disruption and Inflammation.

Since ancient times, various herbs have been used in Asia, including Korea, China, and Japan, for wound healing and antiaging of the skin. In this study, we manufactured and chemically analyzed a novel distillate obtained from a fermented mixture of nine anti-inflammatory herbs (Angelica gigas, Lonicera japonica, Dictamnus dasycarpus Turcz., D. opposita Thunb., Ulmus davidiana var. japonica, Hordeum vulgare var. hexastichon Aschers., Xanthium strumarium L., Cnidium officinale, and Houttuynia cordata Thunb.). The fermentation of natural plants possesses beneficial effects in living systems. These activities are attributed to the chemical conversion of the parent plants to functional constituents which show more potent biological activities. In our current study, the distillate has been manufactured after fermenting the nine oriental medical plants with Lactobacillus fermentum, followed by distilling. We analyzed the chemical ingredients involved in the distillate and evaluated the effects of topical application of the distillate on ultraviolet B (UVB)-induced skin damage in Institute of Cancer Research (ICR) mice. Topical application of the distillate significantly ameliorated the macroscopic and microscopic morphology of the dorsal skin against photodamage induced by UVB radiation. Additionally, our current results showed that topical application of the distillate alleviated collagen disruption and reduced levels of proinflammatory cytokines (tumor necrosis factor alpha and interleukin 1 ß expressions) in the dorsal skin against UVB radiation. Taken together, our current findings suggest that the distillate has a potential to be used as a material to develop a photoprotective adjuvant.

In vitro metabolism of sunscreen compounds by liquid chromatography/high-resolution tandem mass spectrometry.

RATIONALE: Exposure to UV light can induce adverse effects on human health, such as photo-aging, immunosuppression, and cancer. Sunscreens are used to prevent the absorption of UV rays, but certain UV-filtering compounds have been shown to disrupt endocrine systems or act as carcinogens. To assess the effects of the exposure to such compounds, it is important to study the pathways by which they are biotransformed in the body. METHODS: Liquid chromatography coupled to high-resolution tandem mass spectrometry (LC/HRMS/MS) was employed to evaluate the oxidative metabolism and, specifically, the formation of reactive metabolites of six active ingredients commonly used in sunscreen formulations: oxybenzone, avobenzone, homosalate, octisalate, octocrylene, and octinoxate. In vitro incubations were performed with human and rat liver microsomes in the presence of ß-nicotinamide adenine dinucleotide phosphate and glutathione. An LC/HRMS/MS method was developed to identify metabolites employing a biphenyl reversed-phase column for separating parent molecules, metabolites, and glutathione (GSH) adducts. RESULTS: Each tested compound resulted in the formation of several metabolites, including at least one GSH adduct. Compounds containing ester groups were hydrolyzed, and some metabolites of the free acid forms were also detected. High-resolution MS/MS data was crucial for the structural elucidation of metabolites and GSH adducts. Fragmentation pathways were proposed for all parent compounds, as well as each described metabolite and adduct. CONCLUSIONS: The results of this study will help better understand the metabolism and detoxification pathways of these xenobiotics.

Bioinspired biomolecules: Mycosporine-like amino acids and scytonemin from Lyngbya sp. with UV-protection potentialities.

Since the beginning of life on Earth, cyanobacteria have been exposed to natural ultraviolet-A radiation (UV-A, 315-400 nm) and ultraviolet-B radiation (UV-B, 280-315 nm), affecting their cells' biomolecules. These photoautotrophic organisms have needed to evolve to survive and thus, have developed different mechanisms against ultraviolet radiation. These mechanisms include UVR avoidance, DNA repair, and cell protection by producing photoprotective compounds like Scytonemin, carotenoids, and Mycosporine-like amino acids (MAAs). Lyngbya marine species are commercially important due to their secondary metabolites that show a range of biological activities including antibacterial, insecticidal, anticancer, antifungal, and enzyme inhibitor. The main topic in this review covers the Lyngbya sp., a cyanobacteria genus that presents photoprotection provided by the UV-absorbing/screening compounds such as MAAs and Scytonemin. These compounds have considerable potentialities to be used in the cosmeceutical, pharmaceutical, biotechnological and biomedical sectors and other related manufacturing industries with an additional value of environment friendly in nature. Scytonemin has UV protectant, anti-inflammatory, anti-proliferative, and antioxidant activity. MAAs act as sunscreens, provide additional protection as antioxidants, can be used as UV protectors, activators of cell proliferation, skin-care products, and even as photo-stabilizing additives in paints, plastics, and varnishes. The five MAAs identified so far in Lyngbya sp. are Asterina-330, M-312, Palythine, Porphyra-334, and Shinorine are capable of dissipating absorbed radiation as harmless heat without producing reactive oxygen species.

Occurrence of antibiotics, estrogenic hormones, and UV-filters in water, sediment, and oyster tissue from the Chesapeake Bay.

Globally, the occurrence of contaminants of emerging concern (CECs) in the environment has raised critical questions on ecological and human health, but few efforts have focused on the Chesapeake Bay, the largest estuary in the United States. Here, 43 antibiotics, 3 estrogenic hormones, and 5 ultraviolet-filters (UV-filters), which are active ingredients in a variety of personal care products, were measured in water, sediment, and oyster tissue from 14 sites along the Eastern Shore of the Chesapeake Bay in Maryland. Fluoroquinolone, macrolide, and sulfonamide antibiotics were detected in water samples. As both human- and animal-labeled antibiotics were found, wastewater effluent and agricultural runoff were identified as potential sources. The highest aqueous-phase concentrations were recorded for norfloxacin (94.1 ng/L), enrofloxacin (17.8 ng/L), sulfamethoxazole (14.8 ng/L), and clarithromycin (9.7 ng/L). Estrone and four UV-filters, namely 2-ethylhexyl-4-methoxycinnamate, benzophenone-3, homosalate, and octocrylene, were frequently detected in Chesapeake Bay water (93-100%), sediment (100%), and oyster tissue (79-100%). High sediment-phase concentrations of estrone (58.4 ng/g) and 17ß-estradiol (11.5 ng/g) were detected at the mouth of the Manokin River. Homosalate and benzophenone-3 were present at concentrations as high as 187.9 and 113.7 ng/L in water, 74.2 and 10.8 ng/g in sediment, and 158.3 and 118.0 ng/g in oyster tissue, respectively. These results demonstrate the ubiquitous presence of CECs in the Chesapeake Bay, confirm UV-filter bioaccumulation in oysters, and suggest the need for improved CEC removal during municipal wastewater treatment and agricultural waste management within the Chesapeake Bay watershed.

Baicalin and berberine ultradeformable vesicles as potential adjuvant in vitiligo therapy.

0.5-1% of the world's population is affected by vitiligo, a disease characterized by a gradual depigmentation of the skin. Baicalin and berberine are natural compounds with beneficial activities, such as antioxidant, anti-inflammatory and proliferative effects. These polyphenols could be useful for the treatment of vitiligo symptoms, and their efficacy can be improved by loading in suitable carriers. The aim of this work was to formulate and characterize baicalin or berberine loaded ultradeformable vesicles, and demonstrate their potential as adjuvants in the treatment of vitiligo. The vesicles were produced using a previously reported simple, scalable method. Their morphology, size distribution, surface charge and entrapment efficiency were assessed. The ability of the vesicles to promote the permeation of the polyphenols was evaluated. The antioxidant and photoprotective effects were investigated in vitro using keratinocytes and fibroblasts. Further, the stimulation of melanin production and tyrosinase activity in melanocytes after treatment with the vesicles were assessed. Ultradeformable vesicles were small in size, homogeneously dispersed, and negatively charged. They were able to incorporate high amounts of baicalin and berberine, and promote their skin permeation. In fact, the polyphenols concentration in the epidermis was higher than 10%, which could be indicative of the formation of a depot in the epidermis. The vesicles showed remarkable antioxidant and photoprotective capabilities, presumably correlated with the stimulation of melanin production and tyrosinase activity. In conclusion, baicalin or berberine ultradeformable vesicles, and particularly their combination, may represent promising nanosystem-based adjuvants for the treatment of vitiligo symptoms.

Urinary concentrations of benzophenone-type ultra violet light filters and reproductive parameters in young men.

BACKGROUND: Benzophenone (BP)-type ultraviolet (UV) light filters are chemicals frequently added to personal care products, insect repellents, sunscreens, and beverage and food packaging to diminish the harmful effects of UV sunlight on human skin or foodstuffs. BP-type UV filters have shown negative effects on male reproduction function in in vitro and animal models, but human epidemiologic studies are limited. The goal of this study was to examine associations between urinary concentrations of BP-type UV filters and semen quality and reproductive hormone levels. METHODS: This is a cross-sectional study with 215 young university students (18-23 years old) recruited between 2010 and 2011 in Southern Spain (Murcia Region). All men provided a urine, blood and semen sample on a single day. Urinary concentrations of 2,4-dihydroxybenzophenone (BP-1); 2,2',4,4'-tetrahydroxybenzophenone (BP-2); 2-hydroxy-4-methoxybenzophenone (BP-3); 2,2'-dihydroxy-4-methoxybenzophenone (BP-8) and 4-hydroxybenzophenone (4OH-BP) were measured by dispersive liquid-liquid microextraction and ultra-high performance liquid chromatography with tandem mass spectrometry detection. Semen quality was evaluated by measuring volume, sperm counts, motility and morphology. Serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), inhibin B and estradiol (E2). Associations between urinary concentrations of BP-type UV filters and semen quality parameters and reproductive hormone levels were examined using linear regression, adjusting for potential confounders. RESULTS: Ninety-seven percent of the men had detectable urinary concentrations of at least one of the five BP-type UV filters quantified. After adjustment for important covariates (body mass index, smoking status and time of blood sample collection), there was a significant positive association between urinary BP-1 and BP-3 concentrations and serum FSH levels (ß = 0.08, 95%CI: 0.009; 0.15 and ß = 0.04, 95%CI: 0.0002; 0.08, respectively). Urinary BP-1 concentration was also significantly positively associated with T/E2 (ß = 0.04, 95%CI: 0.002; 0.07) and negatively with inhibin b/FSH (ß = -0.11, 95%CI: -0.21; -0.006) ratio. No significant associations were found between other urinary BP-type UV filters and other reproductive hormone levels or between any semen parameters and any of the urinary BP-type UV filters quantified. CONCLUSIONS: Our results suggest that, in young men, urinary BP-type UV filters may be associated with a modest alteration of some reproductive hormones, but the effects we report on reproductive function are likely to be small, and of unclear clinical significance. Further research is needed to replicate these findings in other male populations.

Dual-Prevention for UV-Induced Skin Damage: Incorporation of Melatonin-Loaded Elastic Niosomes into Octyl Methoxycinnamate Pickering Emulsions.

Incorporation of antioxidants into sunscreens is a logical approach, yet co-delivery of them with UV filters is a challenge. Here, we purposed a combination therapy, in which the chemical UV filter, octyl methoxycinnamate, was accumulated on upper skin while the antioxidant, melatonin, can penetrate deeper layers to show its effects. Melatonin-loaded elastic niosomes and octyl methoxycinnamate Pickering emulsion were prepared separately. Lyophilized elastic niosomes were dispersed into the Pickering emulsion to prepare the proposed combination formulation. The characterization studies of the formulations revealed that elastic niosomes can be prepared with tunable nanometer sizes, whereas Pickering emulsions can encapsulate the UV filter in micrometer-sized droplets. Melatonin-loaded elastic niosomes prepared with Tween80/Span80 mixture were 146 nm with a PI of 0.438, and 58.42% entrapment efficiency was achieved. The mean diameter size of the combination formulation was 27.8 µm. Ex vivo permeation studies revealed that 7.40% of octyl methoxycinnamate and 58% of melatonin were permeated through the rat skin while 27.6% octyl methoxycinnamate and 37% of melatonin accumulated in the skin after 24 h. Cell culture studies with real-time cell analyzer showed that the proposed formulation consist of melatonin-loaded elastic niosomes and octyl methoxycinnamate Pickering emulsion had no negative effect on the cell proliferation and viability. According to α,α-diphenyl-ß-picrylhydrazyl free radical scavenging method, the proposed formulation showed as high antioxidant activity as melatonin itself. It is concluded that the proposed formulation would be a promising dual therapy for UV-induced skin damage with co-delivery strategy.

Fotoprotetores bioativos multifuncionais contendo rutina, octil dimetil PABA e avobenzona: caracterização físico-química, funcional e eficácia clínica / Bioactive sunscreens containing rutin, octyl dimethyl PABA and avobenzone: physicochemical, functional and clinical characterization

A exposição crônica à radiação solar pode contribuir para o aparecimento do câncer de pele, sendo o uso de fotoprotetores um fator primordial na prevenção desses efeitos deletérios. Atualmente, substâncias bioativas tais como a rutina têm sido foco de interesse da comunidade científica graças às suas propriedades fotoprotetoras e antioxidantes, que podem promover aumento dos valores de FPS, além de conferir características multifuncionais às formulações. Achados in vitro recentes indicam que a rutina, quando incorporada em emulsões fotoprotetoras óleo em água, promove aumento da atividade antioxidante e aumento do FPS. No entanto, a realização de estudos clínicos é fundamental para confirmar e quantificar esses resultados, já que a metodologia in vitro possui baixa repetibilidade e ausência de correlação com ensaios in vivo, principalmente quando as formulações analisadas apresentam substâncias antioxidantes em sua composição. O objetivo deste estudo foi avaliar pela primeira vez a atividade da rutina frente ao FPS e sua segurança clínica através da comparação de formulações fotoprotetoras contendo rutina 0.1% (w/w), avobenzona 3.0% (w/w) e octil dimetil PABA 8.0% (w/w) com uma preparação similar sem o composto bioativo. Adicionalmente, hidratação cutânea, FPS in vitro e atividade antioxidante da rutina em associação com outros filtros foram investigados. O perfil de segurança das formulações qualificou as fórmulas para os testes de eficácia clínica. O teste de DPPH confirmou a capacidade antioxidante da rutina, demonstrando cerca de 40% de aumento na capacidade de sequestro de radicais livres na presença do composto bioativo. A rutina em combinação com os filtros UV aumentou o FPS clínico de 7.30 ± 0.60 para 12.37 ± 1.13, o que representa cerca de 70% de aumento. Os resultados encontrados provam que a rutina em combinação com outros filtros pode aumentar significativamente o valor do FPS e que a mesma é segura para uso clínico

Unprotected chronic exposure to solar radiation can contribute to premature skin cancer and sunscreens are a key factor to avoid those detrimental effects. Currently, there is a growing interest in the photoprotector and antioxidant potential of bioactive substances, such as rutin, that could help to increase the SPF value and add multifunctional characteristics to the formulations. Recent in vitro findings indicated that rutin, when incorporated in oil-in-water photoprotective emulsions can provide antioxidant activity and SPF increase. However, clinical studies are fundamental to determine this activity duo to in vitro methodology lack of repeatability and correlation between the in vivo data, especially when the analyzed formulas contain antioxidant substances. The aim of this study was to evaluate for the first time to date the rutin in vivo SPF and clinical safety by comparing sunscreens formulations containing rutin 0.1% (w/w), butyl methoxydibenzoylmethane 3.0% (w/w) and octyl dimethylPABA 8.0% (w/w) with a similar bioactive-free preparation. Additionally, skin hydration, in vitro SPF and in vitro antioxidant activity of rutin, in association with the UV filters were investigated. The safety profile of the formulations under sun-exposed skin conditions qualified the formulas for clinical efficacy assays. DPPH test confirmed rutin antioxidant properties, demonstrating about 40% increase in radical scavenging potential when the bioactive compound was present. Rutin in combination with the UV filters increased the clinical SPF from 7.30 ± 0.60 to 12.37 ± 1.13, representing about 70% growth in the SPF value. The results obtained proved that rutin in combination with UV filters can improve the SPF value significantly and is safe for clinical use

Development and evaluation of sunscreen creams containing morin-encapsulated nanoparticles for enhanced UV radiation protection and antioxidant activity.

The objective of present work was to develop novel sunscreen creams containing polymeric nanoparticles (NPs) of morin. Polymeric NPs containing morin were prepared and optimized. The creams containing morin NPs were also prepared and evaluated. Optimized NPs exhibited particle size of 90.6 nm and zeta potential of -31 mV. The entrapment efficiency of morin, within the polymeric NPs, was found to be low (12.27%). Fourier transformed infrared spectroscopy and differential scanning calorimetry studies revealed no interaction between morin and excipients. Transmission electron microscopy and atomic force microscopy revealed that the NPs were spherical in shape with approximately 100 nm diameter. Optimized NPs showed excellent in vitro free radical scavenging activity. Skin permeation and deposition of morin from its NPs was higher than its plain form. Different sunscreen creams (SC1-SC8) were formulated by incorporating morin NPs along with nano zinc oxide and nano titanium dioxide. SC5 and SC8 creams showed excellent sun protection factor values (≈40). In vitro and in vivo skin permeation studies of sunscreen creams containing morin NPs indicated excellent deposition of morin within the skin. Morin NPs and optimized cream formulations (SC5 and SC8) did not exhibit cytotoxicity in Vero and HaCaT cells. Optimized sunscreen creams showed excellent dermal safety. SC5 and SC8 creams demonstrated exceptional in vivo antioxidant effect (estimation of catalase, superoxide dismutase, and glutathione) in UV radiation-exposed rats. The optimized sunscreen creams confirmed outstanding UV radiation protection as well as antioxidant properties.

DNA repair enzymes: an important role in skin cancer prevention and reversal of photodamage--a review of the literature.

The incidence of skin cancer continues to increase annually despite preventative measures. Non-melanoma skin cancer affects more than 1,000,000 people in the United States every year.1 The current preventative measures, such as sunscreens and topical antioxidants, have not shown to be effective in blocking the effects of UV radiation based on these statistics. The level of antioxidants contained in the majority of skin creams is not sufficient to majorly impact free radical damage. Sunscreens absorb only a portion of UV radiation and often are not photostable. In this review article, we present the novel use of exogenous DNA repair enzymes and describe their role in combating photocarcinogenesis and photoaging. Topical application of these enzymes serves to supplement intrinsic DNA repair mechanisms. The direct repair of DNA damage by endogenous repair enzymes lessens rates of mutagenesis and strengthens the immune response to tumor cells. However, these innate mechanisms are not 100% efficient. The use of exogenous DNA repair enzymes presents a novel way to supplement intrinsic mechanisms and improve their efficacy. Several DNA repair enzymes critical to the prevention of cutaneous malignancies have been isolated and added to topical preparations designed for skin cancer prevention. These DNA repair enzymes maximize the rate of DNA repair and provide a more efficient response to carcinogenesis.