Innovative digital solution supporting sun protection and vitamin D synthesis by using satellite-based monitoring of solar radiation.

Public health campaigns advise minimising UV radiation (UVR) exposure to prevent skin cancer and precancer, e.g. actinic keratosis (AK). A 3-day clinical field study, in Brazil, was performed to evaluate the mobile app Sun4Health® by siHealth Ltd. The app performs real-time monitoring of both erythemal and vitamin D-effective solar radiation doses using satellite data, enabling personalised recommendations on optimal sun exposure time and sunscreen use. When coupled to a wearable device, the app also provides body-site specific recommendations ("3D" version). 59 healthy volunteers were randomised into 3 groups, each given a different app providing: (1) ultraviolet index only (control app), (2) personalised recommendations and sun overexposure alerts (Sun4Health® app), (3) as (2) but connected via Bluetooth to a wearable device to monitor sun exposure in 3D (Sun4Health®-3D app). Participants were offered sunscreens (SPF 30 and 50) to use at their discretion. Erythema, quantified by reflectance spectroscopy, was assessed daily in the mornings and evenings on six body sites. Serum vitamin D (25(OH)D3) was measured before and after the study. Mean increase of erythema (Mexameter® units ± SD) of all exposed body sites combined over 3 days showed 55.76 ± 47.47 for group 1, 40.27 ± 37.91 for group 2 and 37.12 ± 30.69 for group 3 (p < 0.05 for all groups). Mean increase of serum 25(OH)D3 (nmol/l ± SD) showed 1.32 ± 36.49 for group 1, 6.38 ± 21.19 for group 2 and 18.68 ± 35.45 for group 3 (p > 0.05 for all groups). The results show that the Sun4Health® app is safe to use and can modify behaviour to reduce skin erythema (sunburn) yet not decreasing vitamin D status.

Percutaneous Absorption of Sunscreen Filters: Review of Issues and Challenges.

Although skin is a vital barrier to the outside world, it is permeable to certain substances used in topical pharmacotherapy. It is therefore not surprising that other xenobiotics intentionally or accidentally coming in contact with skin can cross the skin barrier. Long before the turn of the millennium, it became clear that sunscreen filters from sunscreen products can be systemically absorbed and detected in urine and plasma. Against this background, we review issues and challenges with safety assessments related to the possible percutaneous absorption of the sunscreen filters. A reference is made to the Regulation (EC) No. 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products (version 1 August 2018) and the concepts of the Maximal Usage Trial (MUsT) and Generally Recognized As Safe and Effective (GRASE), currently discussed in the United States.

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.

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.

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.

Development of a Synthetic Substrate for the in vitro Performance Testing of Sunscreens.

PURPOSE: Polymethylmethacrylate (PMMA) plates generally used for the in vitro testing of sunscreens have failed to yield a satisfactory correlation between the sun protection factor (SPF) in vitro and that in vivo. In the present study, various polymers were investigated as alternative substrates to PMMA plates. PROCEDURES: In total, 14 polymers were tested in terms of ultraviolet (UV) transparency by transmission spectroscopy, and surface properties by contact angle measurement. The polymers that were UV transparent and that showed surface properties similar to human skin were mold-injected in casts with various degrees of roughness to obtain corresponding substrate plates. To assess them, the in vitro SPF of 1 sunscreen was measured on a mold-injected PMMA plate as well as on the proposed polymer plates and compared to the in vivo SPF. RESULTS: Four polymers showed a UV transmittance at 310 nm of more than 50%, as well as a total surface free energy close to the reported value for human skin. Of these, 2 provided an in vitro SPF matching the in vivo SPF contrary to the mold-injected PMMA plate for the tested oil-in-water sunscreen. CONCLUSION: This work demonstrates the possibilities of using alternative polymers for synthetic substrates for in vitro sunscreen testing.

Repartition of oil miscible and water soluble UV filters in an applied sunscreen film determined by confocal Raman microspectroscopy.

Photoprotection provided by topical sunscreens is expressed by the sun protection factor (SPF) which depends primarily on the UV filters contained in the product and the applied sunscreen amount. Recently, the vehicle was shown to significantly impact film thickness distribution of an applied sunscreen and sunscreen efficacy. In the present work, repartition of the UV filters within the sunscreen film upon application is investigated for its role to affect sun protection efficacy. The spatial repartition of an oil-miscible and a water-soluble UV filter within the sunscreen film was studied using confocal Raman microspectroscopy. Epidermis of pig ear skin was used as substrate for application of three different sunscreen formulations, an oil-in-water emulsion, a water-in-oil emulsion, and a clear lipo-alcoholic spray (CAS) and SPF in vitro was measured. Considerable differences in the repartition of the UV filters upon application and evaporation of volatile ingredients were found between the tested formulations. A nearly continuous phase of lipid-miscible UV filter was formed only for the WO formulation with dispersed aggregates of water-soluble UV filter. OW emulsion and CAS exhibited interspersed patches of the two UV filters, whereas the segregated UV filter domains of the latter formulation were by comparison of a much larger scale and spanned the entire thickness of the sunscreen film. CAS therefore differed markedly from the other two formulations with respect to filter repartition. This difference should be reflected in SPF when the absorption spectra of the employed UV filters are not the same. Confocal Raman microspectroscopy was shown to be a powerful technique for studying this mechanism of sun protection performance of sunscreens.

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.

Porcine ear skin as a biological substrate for in vitro testing of sunscreen performance.

PURPOSE: The purpose of the study was to examine the use of skin from porcine ears as a biological substrate for in vitro testing of sunscreens in order to overcome the shortcomings of the presently used polymethylmethacrylate (PMMA) plates that generally fail to yield a satisfactory correlation between sun protection factors (SPF) in vitro and in vivo. PROCEDURES: Trypsin-separated stratum corneum and heat-separated epidermis provided UV-transparent substrates that were laid on quartz or on PMMA plates. These were used to determine surface roughness by chromatic confocal imaging and to measure SPF in vitro of 2 sunscreens by diffuse transmission spectroscopy. RESULTS: The recovered skin layers showed a lower roughness than full-thickness skin but yielded SPF in vitro values that more accurately reflected the SPF determined in vivo by a validated procedure than PMMA plates, although the latter had in part roughness values identical to those of intact skin. Combination of skin tissue with a high roughness PMMA plate also provided accurate SPF in vitro. CONCLUSIONS: Besides roughness, the improved affinity of the sunscreen to the skin substrate compared to PMMA plates may explain the better in vitro prediction of SPF achieved with the use of a biological substrate.

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.