Spectra and photorelaxation of tris-biphenyl-triazine-type UV absorbers: from monomers to nanoparticles.

Water-insoluble organic UV filters like tris-biphenyl-triazine (TBPT) can be prepared as aqueous dispersions of nanoparticles. The particles consist of the respective UV absorber molecules and show strong UV absorbance. Since there is a certain solubility of such UV absorbers in organic solvents, it is possible to measure the absorbance spectrum also in solution, for instance in ethanol or dioxane. The UV spectrum of the aqueous dispersion shows a slight hypsochromic shift of the original band with an additional shoulder at longer wavelengths. For the understanding of the observed changes of UV-Vis spectra of this UV absorber, either dissolved in an organic solvent or dispersed as nanoparticles in water, DFT calculations were carried out with the respective monomer and aggregates of TBPT molecules in the different media. The calculated UV-Vis spectra of isolated, that means dissolved, TBPT molecules in ethanol and in dioxane agree well with experimentally observed ones. The observed changes in the shape of experimental UV-Vis spectra in aqueous dispersion cannot be explained with a solvent effect only. It was found that the studied molecules could form stable energetically favorable π-stacked aggregates, which show UV-Vis spectra in reasonable agreement with those experimentally observed in aqueous dispersion. Such aggregates of TBPT are most likely the reason for the observed additional shoulder in the UV/vis absorbance spectrum. In addition, the mechanism of the photochemical deactivation of excited TBPT molecules was studied in detail with TD DFT in dioxane and in water.

A new visible light absorbing organic filter offers superior protection against pigmentation by wavelengths at the UVR-visible boundary region.

Skin pigmentation by solar ultraviolet radiation (UVR; ~295-400 nm) is well established. More recently, visible light (VL; 400-740 nm) has been shown to induce rapid pigmentation. Such pigmentation is thought to be caused by oxidative stress, which has associations with skin cancer and photoageing. However, the UVR-VL boundary region has been less well studied. The lower back of healthy Fitzpatrick skin type II-IV individuals was irradiated with increasing doses of narrow-band 385 nm and 405 nm radiation. Pigmentation change was measured immediately, 6 h and 24 h post-irradiation using two reflectance spectroscopy devices and visual grading. Pigmentation was dose-dependently increased in all skin types and time points for both spectra. Two sunscreens, both labelled SPF 15 and UVA protective in the EU and USA (but with different Boots star rating in the UK, 2* vs 5*) were compared. Their formulations were the same apart from the addition of a new organic filter bis-(diethylaminohydroxybenzoyl benzoyl) piperazine (BDBP) that absorbs between 350 and 425 nm. The product that lacked BDBP provided minimal protection against pigmentation, but its addition provided almost complete protection. This demonstrates the needs to improve photoprotection at the UVR-visible border and for sunscreens to act as neutral density filters.

The Formula for Best Sunscreen Performance: Beer-Lambert's Law Under the Microscope.

Sunscreens used for the protection of human skin work by attenuating the potentially harmful solar UV radiation. In recent years, the quantitative understanding of this attenuating effect has grown tremendously, enabling model calculations of sunscreen performance. Such calculations are based on the simulation of the UV transmission of the sunscreen film applied on human skin. However, there are 2 prerequisites assumed to hold. The first prerequisite is the applicability of the Beer-Lambert law for sunscreen films, and the second is that the thickness variation of the sunscreen film can be described with a gamma distribution of film heights. There is strong evidence from recent experimental work that both assumptions are correct. For several applications, calculations of sunscreen performance have been shown to be useful, for instance, in the design of new sunscreen formulations aiming for a certain sun protection factor or other characteristics, prediction of pre-vitamin D production in the skin in the presence of sunscreen, in vitro measurement of water resistance, and assessment of the ecotoxicological profile of a sunscreen formulation or the influence of oil polarity on UV-filter absorbance and the consequence for sunscreen performance.

Insights into the stabilization of photolabile UV-absorbers in sunscreens.

Sunscreens are used to protect human skin against harmful UV radiation. Today there is a trend towards high sun protection factors (SPF) and good UVA protection. Methods for the assessment of SPF and UVA protection involve irradiation of the product, and the photostability properties of the sunscreen have an influence on its performance. Sunscreens often contain more than one UV filter. Some photolabile UV absorbers may be stabilized by the presence of other photostable UV-absorbers. Stabilization can be achieved just by a certain optical density due to the presence of such UV-filter substances. However, photostabilization may also be caused by quenching mechanisms, such as singlet-singlet or triplet-triplet energy transfer. Investigation of butyl methoxy dibenzoylmethane and ethylhexyl methoxycinnamate as photolabile sunscreens in the presence of either octocrylene or bis ethylhexyloxyphenol methoxyphenyl triazine showed that both mechanisms may apply. With the systems butyl methoxy dibenzoylmethane plus octocrylene and ethylhexyl methoxycinnamate plus bis ethylhexyloxyphenol methoxyphenyl triazine the quenching mechanism appears to be predominant.

Effect of emollients on UV filter absorbance and sunscreen efficiency.

The idea of increasing the performance of sunscreens without adding more UV-filters is very attractive. Early studies reported an influence of solvents on the absorbing properties of UV-absorbers which was shown to be connected to the solvent polarity. However, the polarity differed a lot between tested solvents and most were unsuitable UV-filter solubilizers. The aim of the present study was to focus exclusively on emollients pertinent for sunscreens and investigate their impact on the performance of UV-filter combinations. The UV absorbance of Bis-ethylhexyloxyphenol Methoxyphenyl Triazine, Ethylhexyl Triazone, Diethylamino Hydroxybenzoyl Hexyl Benzoate, and Ethylhexyl Methoxycinnamate was measured in suncare relevant emollients comprising C12-15 Alkyl Benzoate, Dibutyl Adipate, Caprylic/Capric Triglyceride, Coco-caprylate, Isopropyl Myristate, Dicaprylyl Carbonate. The wavelength of maximum absorbance (λmax) and specific extinction at λmax (E1,1 (λmax)) were assessed for each UV-filter - emollient system. The performance of market relevant UV-filter combinations based on the studied UV-filters was simulated for each emollient with a computational method using the absorbance values measured for each UV-filter - emollient system. The difference in polarity of emollients led to a 2-3 nm bathochromic shift and a variation of the E1,1 (λmax) ranging from 4 to 20% for tested UV-filters. The emollient type showed nearly no influence on the sun protection factor (SPF) of market relevant UV-filter combinations probably due to a different influence an emollient shows on the UVB filters resulting in cancelling of the corresponding effect. Conversely, for all UV-filter combinations the UVA protection decreased with a decrease in the emollient polarity. Whilst the SPF was not impacted by standardly used cosmetic oils, the results advocate to use polar emollients to optimize the UVA protection. This is of advantage since polar emollients better dissolve crystalline UV-filters. From tested emollients, Dibutyl Adipate performed the best for both SPF and PPD factors.

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.

Spectra and Photorelaxation of Hydroxyphenyl-benzotriazole-Type UV Absorbers: From Monomers to Nanoparticles.

Water-insoluble organic UV filters such as 2,2'-methylene-bis-(6-(2H-benzotriazole-2-yl)-4-(1,1,3,3-tetramethylbutyl)-phenol) (MBBT) can be prepared as aqueous dispersions of nanoparticles. The particles consist of the respective UV absorber molecules and show strong UV absorbance. Because there is a certain solubility of such UV absorbers in organic solvents, it is possible to measure the absorbance spectrum in solution also, for instance, in ethanol or dioxane. The UV spectrum of the aqueous dispersion shows a significant bathochromic shift of the long-wavelength band with an additional shoulder. For the understanding of the observed changes of UV-vis spectra of this UV absorber, either dissolved in an organic solvent or dispersed as nanoparticles in water, density functional theory (DFT) calculations were carried out with the respective monomer and aggregates of MBBT molecules in different media. The calculated UV-vis spectra of isolated, that means dissolved, MBBT molecules in ethanol and in dioxane agree well with the experimentally observed ones. The observed changes in the shape and position of experimental UV-vis spectra in aqueous dispersion cannot be explained with the solvent effect alone. It was found that the studied molecules could form stable energetically favorable π-stacked dimers, which show UV-vis spectra in reasonable agreement with those experimentally observed in aqueous dispersion. Such aggregates of MBBT are most likely the reason for the observed bathochromic shift in the UV-vis absorption spectrum. In addition, the mechanism of the photochemical deactivation of the excited MBBT molecules was studied in detail with time-dependent DFT in dioxane and in water. The energetically most favorable pathway for the deactivation of absorbed energy by MBBT occurs through intramolecular enol-keto tautomerization in the first excited singlet state.

Analysis of photokinetics of 2'-ethylhexyl-4-methoxycinnamate in sunscreens.

2'-Ethylhexyl-4-Methoxycinnamate (EHMC), also designated as octinoxate, is an oily UV-absorber used in sunscreens for the protection of human skin against solar UV-radiation and represents one of the most employed UVB absorbers for that application. In water-in-oil emulsions EHMC was adjusted at a constant overall concentration, while changing the EHMC concentration in the oil droplets by adding a non-absorbing oil. In that way the EHMC concentration could be varied at constant optical thickness. Here we show that the kinetics of the photoreaction follows a second-order rate law, in line with the UV-induced [2 + 2]-cycloaddition reaction mechanism known for this UV absorber. The second-order rate constant decreased with higher overall EHMC concentration. This can be explained by the fact, that at higher overall concentration of the UV absorber not every EHMC molecule will absorb a photon due to the increased optical density, so that on average less photons are absorbed per molecule. On the other hand, the rate constant increases with decreasing polarity of the surrounding oil. Since the molar fraction of the trans-isomer of EHMC is augmented at lower polarity, more photons are absorbed in this case, as the strength of the absorption band of the trans-isomer is significantly higher than that of the cis-isomer. In conclusion, our experiments show that a high polarity of the oil phase and a high concentration of EHMC are advantageous for the photostability of this compound.

Crystallization Velocity and UV Performance of Formulations With Oversaturated UV-Filter Content.

Cosmetic oils are used to dissolve crystalline lipophilic UV filters; however, little knowledge exists about the effect of other formulation ingredients. This study investigates the influence of emulsifiers on the recrystallization speed of 4 UV filters and the impact of UV-filter crystal formation on delivered performance. The crystallization pattern of studied UV filters was assessed using X-ray diffractometry, whereas their recrystallization speed in formulations with various emulsifiers was monitored microscopically. UV-filter concentration was above the saturation level to promote recrystallization. Furthermore, to understand the kinetics of recrystallization, the conformer number of each UV-filter was calculated. For the impact on performance, the absorbance of a sunscreen was measured before and after recrystallization of the contained UV filter. This study confirmed the crystallinity of tested UV filters. The emulsifier was shown to influence the UV-filter recrystallization speed in emulsions. Continuous oil phase sunscreens were critical; all UV filters recrystallized promptly in oils and water-in-oil emulsions. Large molecule UV filters showed slowest recrystallization speed explained by a higher number of possible conformers. Finally, this work confirmed the negative impact of crystal formation on the delivered photoprotection of a sunscreen.

The UV/Visible Radiation Boundary Region (385-405 nm) Damages Skin Cells and Induces "dark" Cyclobutane Pyrimidine Dimers in Human Skin in vivo.

The adverse effects of terrestrial solar ultraviolet radiation (UVR) (~295-400 nm) on the skin are well documented, especially in the UVB region (~295-320 nm). The effects of very long-wave UVA (>380 nm) and visible radiation (≥400 nm) are much less known. Sunscreens have been beneficial in inhibiting a wide range of photodamage, however most formulations provide very little protection in the long wave UVA region (380-400 nm) and almost none from shortwave visible wavelengths (400-420 nm). We demonstrate photodamage in this region for a number of different endpoints including cell viability, DNA damage (delayed cyclobutane pyrimidine dimers), differential gene expression (for genes associated with inflammation, oxidative stress and photoageing) and induction of oxidizing species in vitro in HaCaT keratinocytes and in vivo in human volunteers. This work has implications for phototherapy and photoprotection.

On the Validity of Beer-Lambert Law and its Significance for Sunscreens.

The sun protection factor (SPF) is the most important quantity to characterize the performance of sunscreens. As the standard method for its determination is based on clinical trials involving irradiation of human volunteers, calculations of sunscreen performance have become quite popular to reduce the number of in vivo studies. Such simulations imply the calculation of UV transmittance of the sunscreen film using the amounts and spectroscopic properties of the UV absorbers employed, and presuppose the validity of the Beer-Lambert law. As sunscreen films on human skin can contain considerable concentrations of UV absorbers, it is questioned whether the Beer-Lambert law is still valid for these systems. The results of this work show that the validity of the Beer-Lambert law is still given at the high concentrations at which UV absorbers occur in sunscreen films on human skin.

Comparison of ultraviolet A light protection standards in the United States and European Union through in vitro measurements of commercially available sunscreens.

BACKGROUND: The importance of adequate ultraviolet A light (UVA) protection has become apparent in recent years. The United States and Europe have different standards for assessing UVA protection in sunscreen products. OBJECTIVE: We sought to measure the in vitro critical wavelength (CW) and UVA protection factor (PF) of commercially available US sunscreen products and see if they meet standards set by the United States and the European Union. METHODS: Twenty sunscreen products with sun protection factors ranging from 15 to 100+ were analyzed. Two in vitro UVA protection tests were conducted in accordance with the 2011 US Food and Drug Administration final rule and the 2012 International Organization for Standardization method for sunscreen effectiveness testing. RESULTS: The CW of the tested sunscreens ranged from 367 to 382 nm, and the UVA PF of the products ranged from 6.1 to 32. Nineteen of 20 sunscreens (95%) met the US requirement of CW >370 nm. Eleven of 20 sunscreens (55%) met the EU desired ratio of UVA PF/SPF > 1:3. LIMITATIONS: The study only evaluated a small number of sunscreen products. CONCLUSION: The majority of tested sunscreens offered adequate UVA protection according to US Food and Drug Administration guidelines for broad-spectrum status, but almost half of the sunscreens tested did not pass standards set in the European Union.

Liposomogenic UV Absorbers are Water-Resistant on Pig Skin-A Model Study With Relevance for Sunscreens.

An important property of sunscreens is their water resistance after the application on human skin. In this work, the hypothesis that UV absorber molecules which are able to form liposomes, so-called liposomogenic UV absorbers, show better water resistance on a pig skin model than UV-absorbing molecules lacking this ability was tested. The assumption behind is that molecules which can form liposomes are able to integrate into the stratum corneum lipids of the skin. Three different liposomogenic UV absorbers were synthesized and their behavior investigated, leading to the confirmation of the hypothesis. With one of the liposomogenic UV absorbers, it was possible to show the integration of the UV absorber molecules into the bilayers of another liposome consisting of phosphatidylcholine, supporting the assumption that liposomogenic UV absorbers exhibit improved water resistance because they integrate into the skin lipids.

Calculation of the sun protection factor of sunscreens with different vehicles using measured film thickness distribution - Comparison with the SPF in vitro.

The sun protection factor (SPF) depends on UV filter composition, and amount and type of vehicle of the applied sunscreen. In an earlier work, we showed that the vehicle affected the average thickness of sunscreen film that is formed upon application to a skin substrate and that film thickness correlated significantly with SPF in vitro. In the present study, we quantitatively assess the role for sunscreen efficacy of the complete film thickness frequency distribution of sunscreen measured with an oil-in-water cream, an oil-in-water spray, a gel, a water-in-oil, and an alcoholic spray formulation. A computational method is employed to determine SPF in silico from calculated UV transmittance based on experimental film thickness and thickness distribution, and concentration and spectral properties of the UV filters. The investigated formulations exhibited different SPFs in vitro and different film thickness distributions especially in the small thickness range. We found a very good agreement between SPF in silico and SPF in vitro for all sunscreens. This result establishes the relationship between sun protection and the film thickness distribution actually formed by the applied sunscreen and demonstrates that variation in SPF between formulations is primarily due to their film forming properties. It also opens the possibility to integrate the influence of vehicle into tools for in silico prediction of the performance of sunscreen formulations. For this, the use of the Gamma distribution was found to be appropriate for describing film thickness distribution.

New Approach to Develop Optimized Sunscreens that Enable Cutaneous Vitamin D Formation with Minimal Erythema Risk.

Sunscreens protect the skin against erythemal radiation (Eer). But at the same time they reduce the effective radiation dose (EVD) responsible for the formation of previtamin D in the skin. The paper describes a calculation method for optimizing the ratio EVD/Eer behind sunscreens e.g. with SPF 5, 15 and 30 respectively. Taking into account that a majority of people in industrialized countries suffer from a shortage in vitamin D even in summer time, the ratio Evd/Eer is a new and important criterion for the quality of sunscreens. Furthermore the exposure time tvd needed per day for forming the equivalent of the recommended amount of 2000 IU of vitamin D per day for skin type 2 is estimated when sunscreens with different filter compositions are used. In vitro experiments show a significant increase of the conversion of 7-dehydrocholesterol (7-DHC) to previtamin D when exposed to artificial solar radiation behind an experimental sunscreen optimized for previtamin D production compared to a commercial sunscreen having the same SPF.

Scattering particles increase absorbance of dyes--a model study with relevance for sunscreens.

Sunscreens used for the protection of human skin against the harmful effects of solar radiation contain UV absorbers as key ingredients, which are either dissolved in one of the phases of the preparation or, when insoluble, suspended as particles. Although the UV protective effect of particulate UV filters, inorganic and organic, is mainly due to absorption, they scatter UV and visible light. The scattering can have an additional attenuating effect on the incoming radiation by increasing the pathlength of the photons, especially when soluble filters are also present. This is investigated with model systems of dyes and absorbing and non-absorbing particles. The presence of particles causes an increase of the dye absorbance without changing dye concentration or cuvette thickness. It is possible to relate this amplification of dye absorbance to the turbidity of the system. Plots are constructed which allow for a given particle type the representation of all data on one single curve, though measured at different turbidity and cuvette thickness. With that, extrapolations to practical applications of sunscreens are possible.

Suntanning with sunscreens: a comparison with sunbed tanning.

BACKGROUND/PURPOSE: Acquiring a tanned skin, either by sunbathing, sunbed use, or a combination of both, is a desirable objective for many people. The objective here was to compare the ultraviolet (UV) exposure resulting from a 2-week vacation spent sunbathing with sunscreen-protected skin, with that from a typical course of 10 sessions on a sunbed. METHODS: A numerical analysis combining data on sunlight and sunbed UV levels, time spent tanning and spectral absorption properties of different types of sunscreen. RESULTS: The analysis showed that unless a sunscreen provides optimal broad-spectrum protection, a 2-week sunbathing vacation that avoids sunburn on sunscreen-protected skin can result in a higher cumulative UV exposure than a typical 10-session sunbed course. The lowest exposures for a given sun protection factor (SPF) are obtained when sunscreen delivers broad-spectrum protection that approaches the ideal of uniform absorption at all wavelengths throughout the UV spectrum. CONCLUSION: In extreme cases of recreational sun exposure where sunscreens providing suboptimal broad-spectrum protection are used, the UV insult to the skin is likely to result in higher cumulative exposures than commonly employed sunbed practices.

Film thickness frequency distribution of different vehicles determines sunscreen efficacy.

Sun protection factor (SPF) frequently differs between sunscreens containing the same composition of ultraviolet (UV) filters that primarily define sunscreen efficacy. We tested the hypothesis that the thickness frequency distribution of the sunscreen film is also responsible for and can explain the divergence in the measured SPF. For this, we developed a method to measure film thickness from the difference of topography before and after application of of sunscreen on pig ear epidermal membrane. The influence of five vehicle formulations and of application pressure and spreading time on mean thickness ( ), to median ratio, and SPF in vitro was investigated. The vehicle had a significant impact, low vehicle viscosity resulting in a smaller , larger to median ratio, and lower SPF in vitro than high viscosity; continuous oil phase produced the largest and SPF values. A long spreading time reduced and SPF and increased application pressure reduced SPF. There was a positive correlation between and SPF in vitro, underlining the relevance of film thickness for interpreting UV protection differences of formulations with the same filter composition. This work demonstrated a strong influence of vehicle and application conditions on sunscreen efficacy arising from differences in film thickness distribution.

Global state of sunscreens.

The use of sunscreen is embedded in a hierarchy of sun protection strategies consisting primarily of sun avoidance by seeking shade and covering up with clothing. Sunscreens are, however, important means of protection; thus, understanding how they work and knowing their limitations are crucial. This review explains the role of ultraviolet (UV) filters, emollients, emulsifier systems and other components in a sunscreen, as well as trends in formulations in Europe, North America, Latin America, and Asia Pacific. Furthermore, it explains how sunscreen performance in terms of sun protection factor, UVA protection, and other metrics can be simulated. The role of sensory characteristics in assessing and improving compliance is also discussed.In the final chapter, Facts and Fiction, five of the most common myths about sun exposure and sun protection by sunscreen are debunked.

On the assessment of photostability of sunscreens exposed to UVA irradiation: from glass plates to pig/human skin, which is best?

Photostability of suncare products is a great area of interest since several sunscreens on the market are photounstable, and this is primarily a problem concerning the UVA region (320-400 nm). Here we report a comparative study on the photostability assessment of two commercial sunscreens with same SPF, spread onto glass plates or onto full thickness pig ear skin or human/pig SCE membranes, and exposed to 183 kJ/m(2) UVA. Absorbance spectra and lipid peroxidation (measured by TBARS production) were determined. The results indicate: (a) sunscreen performance consequent to UVA exposure is independent of whether it is spread onto a non-biological and chemically inert substrate such as glass, or on biological substrates such as skin/SCE membranes; (b) despite the same SPF, sunscreen performance and photostability can be very different; (c) the data on human SCE membranes are similar to those on pig SCE membranes, indicating the suitability of the latter as a model for human skin. However, since the results obtained using skin membranes, akin to the more realistic conditions of use in vivo, do not substantially differ from those obtained on glass plates, the method proposed here using the latter may be applied for rapid, inexpensive, efficacy screening of photostability of sunscreens. Photostability testing should be a mandatory requirement for safer sunscreen protection products, since the results clearly show that some are still far from perfect.