Optimization of Physicochemical Properties of Chitosan–Gum Arabic Nanoparticles Containing Ziziphora clinopodioides Lam. Extract Using Response Surface Methodology

Abstract

ABSTRACT Ziziphora clinopodioides Lam. extract, as a natural bioactive compound, possesses a wide range of health benefits; however, its inherent instability limits practical applications. To overcome this limitation, nanoparticle‐based delivery systems, particularly chitosan–gum arabic nanoparticles, were employed. The aim of this study was to evaluate the effects of varying concentrations of chitosan (3–9 mg/mL), Z. clinopodioides L. extract (3–9 mg/mL), and gum arabic (0.5–1.5 mg/mL), on the physicochemical characteristics of chitosan–gum arabic nanoparticles containing the extract, using a two‐step emulsion–ionic gelation approach. Key parameters, including particle size, zeta potential, and encapsulation efficiency, were assessed by examining both individual and interactive effects. The process was optimized using response surface methodology (RSM) with a Box–Behnken design. The FTIR and XRD analyses were conducted to characterize the nanoparticles. Nanoparticle sizes ranged from 13.90 to 1722.75 nm, while the zeta potentials ranged from 1.63 to 46.67 mV, and the encapsulation efficiencies ranged from 20.51% to 63.66%. Notably, increasing the extract concentration reduced the encapsulation efficiency, while increasing particle size and zeta potential. Higher chitosan concentrations increased nanoparticle zeta potential. In contrast, increasing gum arabic concentration enhanced the encapsulation efficiency. The results demonstrated significant interaction effects among the formulation parameters across all measured responses. Optimal concentrations of chitosan, extract, and gum arabic were determined to be 9, 4.90, and 1.5 mg/mL, respectively, yielding a particle size of 50 nm, a zeta potential of 5.86 mV, and an encapsulation efficiency of 60.63%. The FTIR and XRD analyses confirmed proper encapsulation of the extract. These findings highlight the critical effects of studied parameters on practical characteristics of chitosan–gum arabic nanoparticles loaded with Z. clinopodioides L. extract.