Abstract
Sunscreens are a cornerstone of skin cancer prevention; however, currently available sunscreens have limitations. Concerns regarding current organic sunscreen agents include photodegradation, potential disruption of endocrine pathways, and paradoxical generation of damaging reactive oxygen species (ROS). Recent studies by the FDA have shown that organic sunscreens permeate into systemic circulation at levels warranting further safety testing, highlighting the importance of investigating alternative strategies for safe and effective photoprotection. Towards this goal, we previously conducted high-throughput screening of natural compounds for photoprotective potential, quantifying UV spectral absorbance, photostability, cytotoxicity, and ROS generation. From a pilot set of 915 compounds, we prioritized 11 candidates of interest for confirmatory photostability testing and follow-on in vitro SPF testing at 5wt% in P2 formulation. Top performers were diosmin (DIO; SPF 2.7), isoliquiritigenin (IQL; SPF 2.5), ferulic acid (FA; SPF 3.1), and cytisine (CYT; SPF 6.3). To create a broad-spectrum formulation, these agents were assessed individually and in combination for in vitro SPF and critical wavelength (λcrit), and in vivo in C57BL/6J mice for protection against ultraviolet radiation (UVR)-induced cyclobutane pyrimidine dimer (CPD) formation and irritant contact dermatitis potential. 10% DIO + 10% FA + 5% CYT was the best performer of our test combinations, with a mean in vitro SPF of 48.6 (SD 3.2), λcrit of 373, and 92.4% CPDs blocked (SD 3.5%). Other promising combinations utilizing varying concentrations of FA and CYT with DIO or IQL also demonstrated λcrit>370 and SPF>15, i.e. the FDA minimum requirements for decreasing the risk of skin cancer. None of the combinations induced irritant dermatitis as assessed by gross and histologic examination after 5 repeated applications to shaved dorsal skin every 2 days. Collectively, these data demonstrate proof of concept for high throughput screening as a method of identifying candidate alternative sunscreen agents toward the formulation of a natural product-based sunscreen.
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