Evaluation of antioxidant-enriched cream formulations and their clinical effects in mild to moderate atopic dermatitis

Topical antioxidant-containing creams have been investigated as adjunctive treatments for atopic dermatitis, but clinical efficacy remains inconsistent. In this study, a plant extract mixture containing epigallocatechin gallate, kaempferol, quercetin, and phlorizin was incorporated into two different base formulations and compared with their respective vehicles using ex vivo, in vitro and in vivo approaches. Skin penetration was assessed by confocal Raman microscopy, formulation structure by multiphoton microscopy and clinical efficacy in patients with moderate atopic dermatitis using clinical scores, non-invasive biophysical measurements, and laser scanning microscopy. Despite significant differences in cutaneous penetration between formulations, no clinically relevant differences were observed between antioxidant-containing creams and their vehicles. The water-in-oil emulsion showed a non-significant trend toward greater improvement in pruritus and SCORAD, likely related to occlusive properties, but was not superior to the lighter formulation. Laser scanning microscopy did not demonstrate antioxidant-specific effects. Instead, formulation-dependent effects were observed, with the lighter cream tending to support deeper epidermal recovery, while more occlusive formulations mainly improved stratum corneum hydration. Overall, antioxidant enrichment did not confer additional clinical benefit beyond vehicle effects under the conditions studied. The findings highlight the dominant role of the base formulation and suggest that future studies should optimize formulation design and carefully consider disease severity to detect effects beyond vehicle-related improvements.