Development of Salvia officinalis–Based Self-Emulsifying Systems for Dermal Application: Antioxidant, Anti-Inflammatory, and Skin Penetration Enhancement

Background/Objectives: The present study focused on the formulation and evaluation of novel topical systems containing Salvia officinalis (sage), emphasizing their antioxidant and anti-inflammatory properties. Sage, rich in carnosol, offers considerable therapeutic potential, yet its low water solubility limits its effectiveness in traditional formulations. The aim of our experimental work was to improve the solubility and thus bioavailability of the active ingredient by developing self-nano/microemulsifying drug delivery systems (SN/MEDDSs) with the help of Labrasol and Labrafil M as the nonionic surfactants, Transcutol HP as the co-surfactant, and isopropyl myristate as the oily phase. Methods: The formulations were characterized for droplet size, zeta potential, polydispersity index (PDI), encapsulation efficacy, and stability. The composition exhibiting the most favorable characteristics, with particle sizes falling within the nanoscale range, was incorporated into a cream and a gel, which were compared for their textural properties, carnosol penetration, biocompatibility and efficacy. Results: Release studies conducted using Franz diffusion cells demonstrated that the SNEDDS-based cream achieved up to 80% carnosol release, outperforming gels. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) test and enzyme-linked immunosorbent assays (ELISA) showed strong efficacy, with an in vivo carrageenan-induced rat paw edema model revealing that the SNEDDS-based cream significantly reduced inflammation. Conclusions: These findings highlight the potential of SNEDDS-enhanced topical formulations in improving therapeutic outcomes. Further research is warranted to confirm their long-term safety and efficacy.