Abstract: Several of most common dermatoses worldwide, e.g., psoriasis and atopic dermatitis,\nare worsened in their clinical picture when the skin is regularly exposed to an increased air pollution\nlevel, e.g., particulate matter. This is explainable by the activation of the aryl hydrocarbon receptor\n(AhR) in the skin, which results in an increased release of proinflammatory cytokines and matrix\nmetalloproteinases. Symurban is a competitive AhR antagonist and thus allows the effective protection\nof skin. In order to improve its dermal bioavailability as a poorly soluble active agent (0.25 microg/mL),\nnanocrystals were prepared and evaluated. Nanocrystals are pure active crystals reduced in particle\nsize to the submicron range of 100 to 1000 nm. They feature the properties of nanocrystals, such as\nincreased saturation solubility and dissolution velocity, without having to be declared as nanomaterial.\nProduction methods and parameters were systematically investigated. Wet bead milling at 2000 rpm\nfor 30 min yielded the best results.Az-average of 280nmwas achieved for a 10% Symurban suspension\nwith a polydispersity index of 0.20, indicating a narrowsize distribution. For the long-term stabilization\nof the nanocrystal suspension, the performance of 15 surfactants of different categories and HLB\nvalues were investigated and evaluated. It was found that non-ionic surfactants in general were\nbetter able to stabilize the system than anionic or amphoteric surfactants. Highest stability of over 12\nmonths at 25 Degree C was achieved with 2% Plantacare 810 UP, an ECOCERT surfactant with high skin\ntolerance. The suspension was also chemically long-term stable with >97% of remaining Symurban\nover 12 months. The saturation solubility of Symurban as nanocrystals was significantly increased\nfrom 0.25 to 2.9 micro g/mL, which corresponds to a factor of >11. In a case study of one male volunteer\nwith healthy skin conditions, penetration profiles of Symurban nanocrystal hydrogel and commercial\nanti-pollution serum containing an identical amount of Symurban were determined and compared.\nAfter 20 min of exposure, the relative Symurban concentration in the deeper skin layers (tape 19-30)\nwas more than two times higher for nanocrystal hydrogel (16%) than the commercial serum (7%).\nThese results suggest that nanocrystals are a promising delivery system for the poorly soluble\nanti-pollution agent Symurban.
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