Several of most common dermatoses worldwide, e.g., psoriasis and atopic dermatitis, are worsened in their clinical picture when the skin is regularly exposed to an increased air pollution level, e.g., particulate matter. This is explainable by the activation of the aryl hydrocarbon receptor (AhR) in the skin, which results in an increased release of proinflammatory cytokines and matrix metalloproteinases. Symurban is a competitive AhR antagonist and thus allows the effective protection of skin. In order to improve its dermal bioavailability as a poorly soluble active agent (0.25 µg/mL), nanocrystals were prepared and evaluated. Nanocrystals are pure active crystals reduced in particle size to the submicron range of 100 to 1000 nm. They feature the properties of nanocrystals, such as increased saturation solubility and dissolution velocity, without having to be declared as nanomaterial. Production methods and parameters were systematically investigated. Wet bead milling at 2000 rpm for 30 min yielded the best results. A z-average of 280 nm was achieved for a 10% Symurban suspension with a polydispersity index of 0.20, indicating a narrow size distribution. For the long-term stabilization of the nanocrystal suspension, the performance of 15 surfactants of different categories and HLB values were investigated and evaluated. It was found that non-ionic surfactants in general were better able to stabilize the system than anionic or amphoteric surfactants. Highest stability of over 12 months at 25 °C was achieved with 2% Plantacare 810 UP, an ECOCERT surfactant with high skin tolerance. The suspension was also chemically long-term stable with >97% of remaining Symurban over 12 months. The saturation solubility of Symurban as nanocrystals was significantly increased from 0.25 to 2.9 μg/mL, which corresponds to a factor of >11. In a case study of one male volunteer with healthy skin conditions, penetration profiles of Symurban nanocrystal hydrogel and commercial anti-pollution serum containing an identical amount of Symurban were determined and compared. After 20 min of exposure, the relative Symurban concentration in the deeper skin layers (tape 19-30) was more than two times higher for nanocrystal hydrogel (16%) than the commercial serum (7%). These results suggest that nanocrystals are a promising delivery system for the poorly soluble anti-pollution agent Symurban.
This is an open access article distributed under the Creative Commons Attribution License
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited