Origanum syriacum oil-loaded carboxymethyl chitosan polyelectrolyte nanoparticles: Box–Behnken design optimization of nano-encapsulation, physicochemical, and therapeutic properties

To optimize the loading of therapeutic Origanum syriacum oil (OSO) into carboxymethyl chitosan polyelectrolyte nanoparticles (PENPs), the Box–Behnken design (BBD) was used to assess the effects of PENPs/oil/TPP ratios on the encapsulation efficiency (EE), targeting achieving maximum EE. The OSO-loaded PENPs (OSO#PENPs) were prepared by an ionotropic gelation process and physicochemically characterized using spectral (FTIR) and microscopic (SEM) techniques. The optimized nanocomposite exhibited an EE of 82.69%, a Zeta potential of − 23.32 mV, and a particle size of 131 nm. The OSO release curve exhibited a characteristic biphasic pattern started by an initial burst release followed by a sustained and controlled release phase. Interestingly, the bactericidal activity of OSO#PENPs, with minimal inhibitory and bactericidal concentrations (MIC/MBC) values of 10.25 ± 0.2/5.21 ± 0.3 µg/mL against S. aureus, surpasses that of its precursors (OSO and PENPs) and the clinical antibiotic (ampicillin, Am) (MBC/MIC = 64.5 ± 1.5/ 32.25 ± 0.8 µg/mL). MTT results indicated a dose-dependent effect of synthesized OSO#PENPs on MCF-7 cells, with an IC₅₀ value of 11.1 ± 0.71 μg/mL and a total apoptosis level of 39.85%. OSO#PENPs had much higher cytotoxicity against MCF-7 cells than its precursors. These outcomes indicated the potential of OSO#PENPs as an effective alternative for both traditional antimicrobial and anticancer therapies.