Role of Ozonated Olive Oil in Modulating Skin Permeation and Biological Activities of Topical Microemulsions

Ozonated vegetable oils represent a safe and effective approach to ozone therapy, though further validation is needed, particularly when integrated with nanotechnology. This study developed microemulsions containing ozonated olive oil through a pseudoternary phase diagram and incorporated cinnamon essential oil for its antioxidant and tyrosinase inhibitory properties. Formulations with a low surfactant content were selected based on their isotropic appearance, droplet sizes below 16 nm, polydispersity indices below 0.22, pH values around 4.8, Newtonian behavior, and high physical stability. Their biological performance was evaluated through antioxidants, tyrosinase inhibition, cytotoxicity, and chorioallantoic membrane assays, as well as skin permeation and FTIR analyses. Ozonated formulations exhibited strong tyrosinase inhibition (>77%) and significantly higher antioxidant capacity than non-ozonated systems, while the latter showed negligible inhibitory activity (<12%). Incorporating cinnamon essential oil into the ozonated microemulsion reduced its cytotoxicity and improved cytocompatibility, while the formulations showed no detectable irritation in the HET-CAM assay. Skin permeation tests revealed enhanced diffusion, attributed to lipid extraction and structural interactions within the stratum corneum. Overall, ozonated olive oil microemulsions enhanced the permeation, antioxidant, and tyrosinase inhibition activities of incorporated actives, suggesting their potential as stable, biocompatible, multifunctional topical systems for aesthetic applications such as melasma and photoaging.