Solid Lipid Nanoparticles (SLN) have been prepared by high-pressure homogenization and optimized in order to protect ferulic acid from Ferula assa-foetida L. extract. The influence of lipid and surfactant concentration on the mean particle size (Z-Ave), polydispersity index (PDI), and zeta potential (ZP) of SLN was analyzed. In addition, other parameters for the preparation of ferulic acid-loaded nanoparticles, such as extract concentration and variable parameters for the synthesis method used (e.g., pressure), were adjusted to obtain the smallest particle size and polydispersity index, as well as the highest value for zeta potential, which are characteristic of the stable SLN. The established formulation obtained from the optimized synthesis was composed of 6.0 wt.% of the lipid phase and 1.5 wt.% of surfactant, giving stable SLN with Z-Ave, PDI, and ZP values of 163.00 ± 1.06 nm, 0.16 ± 0.01, and −41.97 ± 0.47 mV, respectively. The loading of ferulic acid from Ferula assa-foetida L. extract within the SLN resulted in particles with a mean size of 155.3 ± 1.1 nm, polydispersity index of 0.16 ± 0.01, zeta potential of −38.00 ± 1.12 mV, and encapsulation efficiency of 27%, the latter being quantified on the basis of RP-HPLC analysis. Our findings highlight the added value of SLN as a delivery system for phenolic phytochemical compounds extracted from Ferula assa-foetida L.
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