Curcumin efficacy is limited due to its low water-solubility and absorption, making curcumin nanoparticles (CN) useful alternatives. This study aimed to optimize CN synthesis through wet-milling using Response Surface Methodology (RSM) – Box-Behnken Design (BBD), considering mean particle size, followed by a comparison between CN synthesized under optimum conditions with curcumin. CN presented the least particle size (35.9 ± 0.1 nm) with a polydispersity index (PDI) of 0.0621 ± 0.0093, radical scavenging ability (RSA) of 89.97% ± 0.57, solubility of 10.46 ± 0.03 μg/mL and dissolution rate of 97.9% ± 1.4 under optimum conditions (curcumin solution concentration of 3.73 mg/mL, flow rate of 0.16 mL/min and ultrasonication time of 38.24 min). However, curcumin showed an average particle size of 671.1 ± 0.9 nm, PDI of 0.2060 ± 0.0104, RSA of 78.11% ± 1.05, solubility of 0.96 ± 0.07 μg/mL and dissolution rate of 11.9% ± 1.7, while being more thermodynamically stable. Fourier Transform Infrared (FTIR) spectroscopy demonstrated that both curcumin and CN had an identical chemical structure. X-Ray Diffraction (XRD) and Differential Scanning Calorimetry (DSC) showed lower crystallinity of CN, and microbiological analysis confirmed their stronger antimicrobial activity as compared with curcumin. Our findings revealed that optimizing the synthesis parameters of CN can improve the resulting nanoparticles’ characteristics, supporting their bioavailability and application as antimicrobial and antioxidant agents in food storage.

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