A nozzle simulation chip toward high-throughput formation of curcumin-loaded zein nanoparticles with tunable properties.

Size of nanoparticle (NP) is a crucial factor in determining its applicability to various fields. This study aimed to develop a nozzle chip for the scalable formation of self-assembled curcumin-loaded zein NPs with tunable properties. A four-factor (zein concentration in dispersed phase, ethanol concentration in continuous phase, flow rate ratio, and total flow rate), three-level Box-Behnken design on the measured responses (particle size and polydispersity index [PDI]) was established. The particle size and PDI, ranging from 194.43 to 420.51 nm, and 0.089 to 0.219, respectively, were readily controlled by adjusting four factors. Under the optimal conditions of 6% zein, 0% EtOH, the flow rate ratio of 7, and a total flow rate of 8 mL/min targeting higher production rate, the particle size of 306.02 ± 1.52 nm (mean ± standard deviation) and the PDI of 0.135 ± 0.001 were obtained. High throughput for zein NP production (86.4 g/day) was reached, which was 200 and 960 times higher than using microfluidic and electrospraying techniques, respectively. Curcumin-loaded zein NPs under the abovementioned experimental conditions were successfully prepared via the nozzle chip with the encapsulation efficiency of 64.29% ± 0.29%, a loading capacity of 3.06% ± 0.01%, enhanced stability, and improved in vitro antioxidant properties. Curcumin was primarily released from zein NPs in the simulated intestinal phase. This study demonstrated that the property of self-assembled zein NPs can be tuned by altering the operating parameters using the nozzle simulation chip. The results suggest that this approach has potential for use in the food and pharmaceutical industries, particularly for curcumin encapsulation. PRACTICAL APPLICATION: The fabricated nozzle chip is a promising technology to obtain zein nanoparticles (NPs) with enhanced productivity and narrow particle size distribution. It can be easily adopted to spray drying process. Besides, the nozzle chip shows the potential for the large-scale production of bioactive loaded zein NPs in the food or pharmaceutical industries.