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Nanoencapsulation is an attractive technique used for incorporating essential oils in foods. Thus, our main goal was to formulate a novel nanoemulsion (NE) with nanoscale droplet size and lowest interfacial tension in the oil–water interface, contributing positively to the stability and the enhancement of essential oil potential. Thereby, response surface methodology (RSM), with mixture design was used to optimize the composition of the NE lipid phase. The essential oil combinations were encapsulated through high-pressure homogenization (HPH) with the binary emulsifier system (Tween 80: Gum Arabic). Then, the electrophoretic and physical properties were evaluated. We also conducted a follow-up stability and antimicrobial study that examined the stabilization mechanism of optimal NE. Thereafter, the effect of nanoencapsulation on the essential oil composition was assessed. The RSM results were best fitted into polynomial models with regression coefficient values of more than 0.95. The optimal NE showed a nanometer-sized droplet (270 nm) and lower interfacial tension (~11 mN/m), favoring negative ζ-potential (−15 mV), showing good stability under different conditions—it synergistically enhances the antimicrobial potential. GC-MS analysis showed that the use of HPH affected the active compounds, consistent with the differences in linalool and 2-Caren-10-al content. Hence, the novel nanometric delivery system contributes to food industry fortification.

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Essential-Oil-Loaded Nanoemulsion Lipidic-Phase Optimization and Modeling by Response Surface Methodology (RSM): Enhancement of Their Antimicrobial Potential and Bioavailability in Nanoscale Food Delivery System