Biocompatible Rosmarinus officinalis essential oil-loaded phytosomes for enhanced antioxidant and anticancer performance

• Demonstrating efficient phytosomal encapsulation of rosemary essential oil with high entrapment efficiency, nanoscale stability, and defined molecular interactions confirmed by FTIR analysis. • Establishing enhanced antioxidant activity of the phytosomal formulation compared to free essential oil using the DPPH assay. • Showing improved biological selectivity through reduced cytotoxicity toward normal endothelial cells while maintaining anticancer activity against MCF-7 breast cancer cells. • Evaluating the environmental sustainability of the extraction and formulation process using the Green Analytical Procedure Index (GAPI), offering a balanced discussion of performance versus greenness. Essential oils (EOs) have been widely used in traditional medicine due to their unique properties. However, their use in clinical applications is still limited due to their instability to light and high volatility. Nanocarriers have offered a promising strategy to improve their physicochemical stability. In this study, Rosmarinus officinalis EOs (R.O EOs)-loaded phytosomal nanovesicles were designed and evaluated for antioxidants and anticancer activity. R.O EO-loaded phytosomes were optimized and characterized in terms of particle size, polydispersity index (PDI), zeta potential, recovery, encapsulation efficiency (EE%), and stability. The EO-loaded phytosomes exhibited uniform and stable nanoformulation with an average particle size of 223.3 ± 8.6 nm, a zeta potential of −53.89 mV, and a PDI of 0.22. The encapsulation efficiency was calculated to be 80.1 %, and the phytosomes remained stable over 7 days at 4 °C. Antioxidant activity DPPH assay showed enhanced radical scavenging for the EO-loaded phytosomes (EC 50 = 32.9 μg/mL) compared to free EOs (48.1 μg/mL). Cytotoxicity evaluation revealed improved selectivity of the phytosomal formulation, with IC 50 values of 99.4 μg/mL against MCF-7 cancer cells and 243.4 μg/mL against EA.hy926 normal cells, compared to 68 μg/mL and 125 μg/mL, respectively, for free EOs. These findings suggest that phytosomal encapsulation effectively reduces the volatility of R.O EOs. This reduction enhances their biological performance and improves safety profiles, which makes them promising candidates for antioxidant and anticancer applications.