Ferulic acid photoprotective properties in association with UV filters: multifunctional sunscreen with improved SPF and UVA-PF.

Ultraviolet (UV) radiation stimulates several injurious biological effects on cutaneous tissue, causing, for instance, photocarcinogenesis. Sunscreens are topical products designed to protect the skin against these harmful effects and their use must be encouraged. The addition of antioxidants, as ferulic acid (FA), a phenolic compound from the class of the hydroxycinnamic acids, in sunscreens could improve their sun protection factor (SPF) and prevent inflammatory reactions. Here, the clinical safety and efficacy of an association of ethylhexyl triazone and bis-ethylhexyloxyphenol methoxyphenyl triazine (UV filters) with ferulic acid were assessed. Samples had good skin biocompatibility and presented satisfactory safety profile, even in a sun-exposed condition. A synergic effect between the natural polyphenol and the UV filters was evidenced, as well as, FA increased in vivo SPF in 37% and the UVA protection factor (UVA-PF) in 26%. The in vivo data indicated that FA reinforced the broad-spectrum characteristic of the photoprotective formulations. Additionally, according to the results from the ex vivo antioxidant test, it is plausible to recommend adjustments on the ex vivo protocol to explicitly determine the positive effects of topical antioxidant ingredients applied over the skin. These results provided a new perspective for the development of multifunctional bioactive sunscreens using FA as a new platform.

Quality by design (QbD), Process Analytical Technology (PAT), and design of experiment applied to the development of multifunctional sunscreens.

Multifunctional formulations are of great importance to ensure better skin protection from harm caused by ultraviolet radiation (UV). Despite the advantages of Quality by Design and Process Analytical Technology approaches to the development and optimization of new products, we found in the literature only a few studies concerning their applications in cosmetic product industry. Thus, in this research work, we applied the QbD and PAT approaches to the development of multifunctional sunscreens containing bemotrizinol, ethylhexyl triazone, and ferulic acid. In addition, UV transmittance method was applied to assess qualitative and quantitative critical quality attributes of sunscreens using chemometrics analyses. Linear discriminant analysis allowed classifying unknown formulations, which is useful for investigation of counterfeit and adulteration. Simultaneous quantification of ethylhexyl triazone, bemotrizinol, and ferulic acid presented at the formulations was performed using PLS regression. This design allowed us to verify the compounds in isolation and in combination and to prove that the antioxidant action of ferulic acid as well as the sunscreen actions, since the presence of this component increased 90% of antioxidant activity in vitro.

Hydrolyzed collagen interferes with in vitro photoprotective effectiveness of sunscreens

ABSTRACT The chronological skin aging is a progressive and natural process with genetic and physiological changes. However, ultraviolet (UV) radiation may accelerate the oxidative stress, generating carcinogenesis and photoaging. Natural compounds and their applications are considered a trend in the cosmetic market. The protein-based film-forming compounds play an important role, once it collaborates for the better distribution of sunscreens on the skin. Here we investigated the in vitro photoprotective effectiveness of sunscreens containing the hydrolyzed collagen associated with UVA, UVB and/or inorganic filters. Sunscreens were developed with octocrylene (7.5%), butyl methoxydibenzoylmethane (avobenzone) (3.0%) and/or titanium dioxide (5.0%), associated or not with the hydrolyzed collagen (3.0%). In vitro photoprotective effectiveness was determined in a Labsphere(r) UV2000S by the establishment of the sun protection factor (SPF) and critical wavelength (nm) values. Physicochemical and organoleptic characteristics were also assayed. The hydrolyzed collagen subjectively improved the formulation sensory characteristics. However, this bioactive compound led to a decrease of the SPF values of the photoprotective formulations containing octocrylene alone and octocrylene + butyl methoxydibenzoylmethane + TiO2. This inadequate interaction may be considered during the development of new sunscreens intended to contain protein-based components.

Gelatin-based microspheres crosslinked with glutaraldehyde and rutin oriented to cosmetics

ABSTRACT Glutaraldehyde (GTA) has been extensively used as a gelatin crosslinking agent, however, new natural ones have been suggested as more biocompatible. Polyphenols are possible candidates and the flavonols, such as rutin (RUT), also exhibit potential synergism with sunscreens and antioxidant agents used in cosmetics. In this work, gelatin microspheres (M0) were obtained and crosslinked with GTA 10 mM (MG) or RUT 10 mM (MR), dissolved in acetone:NaOH 0,01M (70:30 v/v). MG exhibited crosslinking extent of 54.4%. Gelatin, M0, MG and MR did not elicit any signs of skin damage, regarding the formation of erythema, the barrier function disruption and negative interference in the stratum corneum hydration. Oily dispersions containing M0, MG or MR, isolated or combined with benzophenone-3 or octyl methoxycinnamate, suggested that the microspheres, at a 5.0% w/w, had no additional chemical or physical photoprotective effect in vitro. Crosslinking with RUT had occurred, but in a lower degree than GTA. Microspheres had not improved sun protection parameters, although, non-treated gelatin interfered positively with the SPF for both UV filters. The in vivo studies demonstrated that these materials had very good skin compatibility.

Cutaneous biocompatible rutin-loaded gelatin-based nanoparticles increase the SPF of the association of UVA and UVB filters.

The encapsulation of natural ingredients, such as rutin, can offer improvements in sun protection effectiveness. This strategy can provide enhanced flavonoid content and produces an improved bioactive compound with new physical and functional characteristics. As an alternative to common synthetic-based sunscreens, rutin-entrapped gelatin nanoparticles (GNPs) were designed and associated with ethylhexyl dimethyl PABA (EHDP), ethylhexyl methoxycinnamate (EHMC) and methoxydibenzoylmethane (BMDBM) in sunscreen formulations. The purpose of this study was to develop rutin-loaded gelatin nanoparticles and characterize their physicochemical, thermal, functional and safety properties. Rutin-loaded gelatin nanoparticles increased antioxidant activity by 74% relative to free-rutin (FR) solution. Also, this new ingredient upgraded the Sun Protection Factor (SPF) by 48%, indicating its potential as a raw material for bioactive sunscreens. The safety profile indicated that GNPs and glutaraldehyde (GTA) decreased HaCaT cell viability in a concentration/time-dependent manner. However, both blank nanoparticles (B-NC) and rutin-loaded nanoparticles (R-NC) had good performance on skin compatibility tests. These results functionally characterized rutin-loaded nanoparticles as a safe SPF enhancer in sunscreens, especially in association with UV filters.

Particle size and morphological characterization of cosmetic emulsified systems by Optical Coherence Tomography (OCT)

ABSTRACT The physicochemical attributes of emulsified systems are influenced by the characteristics of their internal phase droplets (concentration, size and morphology), which can be modified not only by the formulation components, but also by the analytical methodology employed. Thus, the aim of this work involved the physicochemical characterization of cosmetic emulsions obtained from different surfactants, as well as the introduction of the optical coherence tomography (OCT) as the analytical technique employed for the morphological characterization and particle size determination of the formulations. Three emulsions were prepared, differing at the type and concentration of the surfactant used, and their droplet sizes were evaluated through optical microscopy, laser diffraction and OCT. The microscopic analysis and the laser diffraction techniques provided an average particle size minor than 6.0 µm, not detected by the OCT technique, which could identify only bigger particles of the emulsified systems' internal phase. The results testify that OCT was suitable for the morphological characterization of cosmetic emulsions; however, the technique needs to be improved to ensure a better sensitivity in the analysis of smaller particles.

RESUMO Os atributos físico-químicos de sistemas emulsionados são influenciados pelas características de suas gotículas de fase interna (concentração, tamanho e morfologia), as quais podem ser modificadas não apenas pelos componentes da formulação, mas também pela metodologia analítica empregada. Desta forma, o objetivo deste trabalho envolveu a caracterização físico-química de emulsões cosméticas obtidas a partir de diferentes tensoativos, bem como a introdução da tomografia de coerência óptica (OCT) como a técnica analítica utilizada para a caracterização morfológica e determinação do tamanho de partícula das formulações. Três emulsões foram preparadas, diferindo no tipo e concentração do tensoativo empregado, e seus tamanhos de gotícula foram avaliados por meio das técnicas de microscopia óptica, difração a laser e OCT. As técnicas de microscopia óptica e difração a laser forneceram tamanhos de partícula médios menores de 6.0 µm, não detectados pela técnica de OCT, que permitiu apenas a identificação de partículas maiores pertencentes à fase interna dos sistemas emulsionados. Os resultados reforçam a introdução da OCT como metodologia promissora para a caracterização morfológica de emulsões cosméticas; no entanto, a técnica requer aprimoramento para garantir maior sensibilidade na análise de partículas de menor tamanho.

Ácido ferúlico em protetores solares: desenvolvimento e eficácia multifuncional in vitro, ex vivo e in vivo / Ferulic acid in sunscreens: development and multifunctional effectiveness in vitro, ex vivo and in vivo

A conscientização da população com relação aos malefícios da radiação ultravioleta (UV) levaram à adoção de hábitos preventivos, com destaque para a utilização diária de formulações fotoprotetoras. Ainda que os filtros solares tradicionais sejam efetivos na absorção ou reflexão da radiação UV, sabe-se que a sua atuação contra os radicais livres é limitada, fator que exige a incorporação de compostos antioxidantes às preparações, visando proteção cutânea de excelência. O presente trabalho objetivou o desenvolvimento e avaliação de formulações multifuncionais contendo os filtros solares bemotrizinol e octil triazona, acrescidos do composto bioativo ácido ferúlico - reconhecido pelas suas propriedades antioxidante e fotoprotetora. As formulações foram desenvolvidas de acordo com um delineamento experimental do tipo fatorial (DoE 23) e avaliadas por meio de metodologias in vitro, in vivo e ex vivo para determinação de sua eficácia fotoprotetora e potencial antioxidante. As emulsões foram consideradas estáveis, seguras, com valor de pH biocompatível com a pele e viscosidade aparente adequada ao uso proposto. O delineamento experimental comprovou o potencial antioxidante e fotoprotetor do ácido ferúlico, visto que a presença deste promoveu aumento de até 90% na atividade antioxidante in vitro das formulações, bem como acréscimo de 32% no Fator de Proteção Solar (FPS) in vivo e 24% no Fator de Proteção UVA (UVA-PF). Por meio do ensaio ex vivo, a formulação contendo o ácido ferúlico apresentou tendência em aumentar a atividade antioxidante natural da pele, comparativamente à formulação contendo apenas os filtros solares e à pele não tratada; ademais, houve queda no potencial antioxidante da pele após a exposição à radiação UV, enfatizando a necessidade de proteção cutânea frente aos danos oxidativos. Os resultados comprovaram os efeitos antioxidante e fotoprotetor combinados do ácido ferúlico, em especial quando em sinergismo com filtros solares, tornando o composto bioativo um candidato promissor no desenvolvimento de formulações multifuncionais inovadoras, seguras e eficazes contra os efeitos nocivos decorrentes da exposição solar

The public awareness regarding the harmful effects of ultraviolet (UV) radiation led to preventive habits, especially the daily use of sunscreens. Although traditional solar filters are effective in UV radiation absorption or reflection, it is known that their activity against free radicals is restricted, an aspect that requires the incorporation of antioxidants to preparations, aiming superior skin protection. Here, we developed and evaluated multifunctional formulations containing the sunscreens bemotrizinol and ethylhexyl triazone plus the bioactive compound ferulic acid - known for its antioxidant and photoprotective properties. Formulations were developed according to a factorial experimental design (DoE 23) and evaluated using in vitro, in vivo and ex vivo methods to determine its photoprotective effectiveness and antioxidant potential. The emulsions were considered stable, safe, with pH value biocompatible with the skin and apparent viscosity suitable for the proposed use. The experimental design evidenced the photoprotective and antioxidant potential of ferulic acid, once its presence increased to 90% the in vitro antioxidant activity of the formulations, as well as 32% increase in the in vivo Sun Protection Factor (SPF) and 24% increase in the UVA Protection Factor (UVA-PF). Through the ex vivo assay, the formulation containing ferulic acid tended to increase the natural antioxidant activity of the skin, compared to the formulation containing only UV filters or the untreated skin; moreover, there was a decrease in the antioxidant potential of the skin after UV radiation exposure, emphasizing the need for skin protection against oxidative damage. The results confirmed the antioxidant and photoprotective effects of ferulic acid, especially when in synergy with UV filters, making the bioactive compound a promising candidate in the development of innovative, safe and effective multifunctional formulations against the harmful effects of sun exposure

Functional photostability and cutaneous compatibility of bioactive UVA sun care products.

Sunscreens are the most-established approach for photoprotection. The strategy of providing antioxidant properties to sun care products by addition of natural and potent anti-free radical compounds has led to the development of bioactive sunscreens, able to neutralize the harmful effects of ultraviolet (UV) radiation. UVA filters, such as benzophenone-3 (BP) and butyl methoxydibenzoylmethane (BMDBM), can exhibit photodegradation which limits the development of broad spectrum sunscreens. Previous research verified that rutin interacts with filters incorporated in sunscreens. In this work, we focused on the development and evaluation of the efficacy of the sunscreens containing either BP or BMDBM with and without rutin. The addition of rutin to the UVA filters afforded antioxidant properties to the formulations and they were considered safe for human use. Additionally, rutin in combination with either BP or BMDBM increased the antioxidant activity about 40 times when compared with the UVA filters alone. Remarkably, the addition of rutin 0.1% (w/w) to BP 6.0% (w/w) raised the SPF from 24.3±1.53 to 33.3±2.89. In conclusion, these findings demonstrated that the addition of rutin into sunscreens can markedly improve the antioxidant properties of the formulation as well as photostabilize some of the UVA filters.

Avaliação do fator de proteção solar (FPS) in vitro e perfil reológico de fotoprotetores comerciais infantis / Assessment of in vitro Sun Protection Factor (SPF) and rheological profile of commercial infant sunscreens

A pesquisa tem como objetivo a aplicação da transmitância espectral utilizando uma esfera de integração para estimar o Fator de Proteção Solar (FPS) de fotoprotetores comerciais para o uso infantil. Fotoprotetores com FPS 30 (A, B e C), disponíveis comercialmente, foram selecionados para avaliação conforme as seguintes metodologias: valor de pH, perfil reológico, e valor de FPS in vitro por espectroscopia. As amostras A, B e C apresentaram, respectivamente, os seguintes valores de pH: 7.8, 7.4 e 7.0. O perfil reológico identificou os sistemas como semissólidos pseudoplásticos não-Newtonianos, com área de histerese. O teste-T (p < 0.05) foi utilizado para confrontar o FPS alegado (FPS = 30) com o estimado por espectroscopia. Estudos in vitro foram considerados de grande importância para a área cosmética, podendo corroborar, previamente, a realização dos estudos de eficácia in vivo. De acordo com os resultados, as amostras A, B e C apresentaram valores de FPS sem diferença estatisticamente significativa, quando comparados àqueles citados nos rótulos. A transmitância espectral utilizando esfera de integração provou ser uma metodologia conveniente, rápida e reprodutível para a avaliação estimada do FPS.

This research focused on the measurement of spectral transmittance using an integrating sphere to estimate the Sun Protection Factor (SPF) of commercial sunscreens oriented for child use. Commercially available SPF 30 sunscreens (A, B and C) were selected and assessed by the following methodology: pH measurement; rheological profile analysis; and in vitro SPF estimation by spectroscopy. Samples A, B and C exhibited, respectively, pH values of 7.8, 7.4 and 7.0. The rheological profile identified the systems as pseudoplastic non-Newtonian semisolids with hysteresis loops. The t-test (p < 0.05) was used to confront the claimed SPF (SPF = 30) with that estimated by spectroscopy. In vitro tests are considered of utmost importance in the cosmetic , since their results may be used to validate submission to subsequent in vivo efficacy experiments. According to our results, sunscreens A, B and C generated SPF values without any significant difference from those claimed on the commercial sunscreen labels. The measurement of spectral transmittance with an integrating sphere proved to be a convenient, fast and reproducible method for SPF estimation.

Desenvolvimento e avaliação de produtos cosméticos para a higiene capilar contendo tensoativos "não-sulfatados" / Development and assessment of hair-cleansing cosmetic formulations containing non-sulfate surfactants

Produtos cosméticos para a higiene capilar promovem a remoção de gordura, suor, poeira, células mortas, micro-organismos e resíduos de outros cosméticos do couro cabeludo e do cabelo. Com esta finalidade, foi proposto o desenvolvimento e avaliação da estabilidade de formulações contendo tensoativos primários não sulfatados associados separadamente com diferentes agentes de consistência (Myrj® 6000, NovethixTM L-10 e Carbopol® Ultrez 20). Dentre os seis tensoativos "não sulfatados" avaliados, dois foram selecionados (Plantapon® LGC Sorb e Sensactive® C30) conforme critérios de avaliação da viscosidade e da formação de espuma. Seis formulações foram desenvolvidas, com combinações distintas entre os tensoativos selecionados e os diferentes agentes de consistência (sem a adição intencional de cloreto de sódio), com posterior estudo de estabilidade em variadas condições de armazenamento. Durante os estudos de estabilidade acelerada, as formulações contendo os agentes de consistência Myrj® 6000 ou NovethixTM L-10 não apresentaram estabilidade adequada. Ao final do estudo de estabilidade normal, as formulações remanescentes, contendo Carbopol® Ultrez 20, mantiveram as características organolépticas e desempenho adequado quanto à viscosidade, comprovando a eficiência deste polímero, mesmo em formulações com grandes quantidades de tensoativos "não sulfatados" e eletrólitos.

Cosmetic products for hair cleansing promote the removal of grease, sweat, dirt, dead cells, microorganisms and residues of other cosmetics from the skin, scalp and hair. In this context, it was decided to develop and assess the stability of formulations containing various non-sulfate primary surfactants, combined separately with three different consistency agents (Myrj® 6000, NovethixTM L-10 and Carbopol® Ultrez 20). Among the six non-sulfate surfactants tested, two were selected (Plantapon® LGC Sorb and Sensactive® C30) by viscosity and foam formation criteria. Thus, 6 formulations were developed, with distinct combinations of the 2 selected surfactants and 3 consistency agents (without the intentional addition of sodium chloride), and subsequently their stability under various storage conditions was studied. In the short-term stability study, formulations containing the consistency agents Myrj® 6000 or NovethixTM L-10 did not show adequate stability. At the end of the full-length stability study, the remaining formulations, containing Carbopol® Ultrez 20, maintained their organoleptic characteristics and good viscosity, proving the efficiency of this polymer, even in formulations with large amounts of non-sulfate surfactants and electrolytes.