The Challenge

Sunscreens can prevent skin cancer and protect the skin from sunburn and other UV damage, along with providing other sun protective measures. Many products on the market do a fantastic job protecting consumers when they hit the beach, lake or hiking trail. The first part of this blog describes the protective effect of sunscreen formulation and ingredients as well as in silico methods to predict their efficacy and environmental “friendliness:”

 

 

Increasing numbers of physicians are recommending sunscreen as part of a daily skincare routine. As a result, a wider range of consumers is using sunscreens more frequently. However, there is increasing concern that some active ingredients utilized in sunscreen are appearing in the bloodstream at higher levels than previously anticipated, potentially opening up risks to human health.¹ This has led to growing pressure to explore alternative sunscreen ingredients to ensure safe, effective and sustainable methods to protect skin.

Impact on the Environment

To ensure product safety, the US Food and Drug Administration (FDA) proposed an update of the requirements for sunscreen ingredients in 2019.¹ With our commitment to harmonizing product, nature and life, BIOVIA Dassault Systèmes is driven to help R&D teams identify and characterize novel sunscreen formulation and ingredients with reduced negative impact on the environment and heightened positive impact on human safety.

Combining the predictive COSMO-RS method² and biological information about the skin, BIOVIA Solvation Chemistry provides a fully mechanistic model to predict the skin penetration rate.³ Skin-penetration simulation is an application of the COSMOperm method.³

What is special and unique about this method is its ability to capture formulation effects explicitly for typical sunscreens formulated as lotions, aerosol sprays, non-aerosol sprays and pump sprays. Even more, this simulation tool can observe permeability differences of sunscreen ingredients between fresh water and saline water, i.e., under different environmental conditions.

Simulating the Impact of Sunscreen Formulation

The following analysis describes the simulation results for widely used active ingredients  – avobenzone, oxybenzone, octocrylene, homosalate, octisalate and octinoxate – studied in a recent clinical trial.¹

There is a striking correlation (R² = 93%) between the maximum plasma concentration in the clinical trial and the skin penetration values for particular ingredients simulated by COSMOperm, as shown in Figure 1, using the respective median values of a given sunscreen formulation. The simulation takes conformers and potential tautomers into account.

 

The effects of the sunscreen formulation matrix play an important role in the simulation. Sunscreens are available as classic lotions or sprays with off-the-shelf sprays available in different variants: aerosol, non-aerosol and pump spray. Figure 2 depicts the variance or maximum absolute differences for the simulated skin penetration rate and the experimental maximum plasma concentration between the different formulations. Moreover, this indicates a very similar trend between skin and blood plasma.

Environmental Influence on the Formulation

A very typical application for sunscreens is a fun day on the beach. However, there might be differences in the accumulative behavior of sunscreen formulation and ingredients based on taking a swim in the fresh water of a local lake vs. saline water in the ocean.  BIOVIA COSMOperm also simulates this. Indeed, statistically significant differences result from the simulations. An increased uptake is observed in saline water, in the worst-case scenario by a factor of 30 (oxybenzone) up to 300 (octocrylene). These values should just describe the general trend, because the mostly lipophilic formulation matrix reduces this effect between fresh and saline water. Additionally, secondary effects might play a role (e.g., deviating swelling effects or pathways), which are not yet taken into account by the simulation. Nevertheless, the tool might provide useful guidance by taking into account a large variety of environmental effects.

The BIOVIA portfolio provides a comprehensive collection of solutions to help guide personal care R&D. BIOVIA Solvation Chemistry, which utilizes the COSMO-RS methodology, can also shed light on the thermodynamic properties of UV filters in different solvents. Such insights can provide much-needed context on how they will behave in the bottle, on the skin or in the water.

Additionally, the Materials Studio Collection in BIOVIA Pipeline Pilot can help expert computational chemists create and share sophisticated workflows with their colleagues at the bench, fostering collaboration and democratizing the power of these models.

 

 

References

1. Matta, M. K.; Florian, J.; Zusterzeel, R.; Pilli, N. R.; Patel, V.; Volpe, D. A.; Yang, Y.; Oh, L.; Bashaw, E.; Zineh, I.; Sanabria, C.; Kemp, S.; Godfrey, A.; Adah, S.; Coelho, S.; Wang, J.; Furlong, L.-A.; Ganley, C.; Michele, T.; Strauss, D. G. Effect of Sunscreen Application on Plasma Concentration of Sunscreen Active Ingredients: A Randomized Clinical Trial. JAMA 2020, 323 (3), 256. https://doi.org/10.1001/jama.2019.20747.

2. Klamt, A. The COSMO and COSMO-RS Solvation Models: COSMO and COSMO-RS. Wiley Interdisciplinary Reviews: Computational Molecular Science 2018, 8 (1), e1338. https://doi.org/10.1002/wcms.1338.

3. Schwöbel, J. A. H.; Klamt, A. Mechanistic Skin Penetration Model by the COSMOperm Method: Routes of Permeation, Vehicle Effects and Skin Variations in the Healthy and Compromised Skin. Computational Toxicology 2019, 11, 50–64. https://doi.org/10.1016/j.comtox.2019.02.004.

4. Schwöbel, J. A. H.; Ebert, A.; Bittermann, K.; Huniar, U.; Goss, K.-U.; Klamt, A. COSMOperm: Mechanistic Prediction of Passive Membrane Permeability for Neutral Compounds and Ions and Its PH Dependence. J. Phys. Chem. B 2020, 124 (16), 3343–3354. https://doi.org/10.1021/acs.jpcb.9b11728.