Ultrasound-driven antisolvent precipitation for engineered naringenin ultrafine crystals with potent xanthine oxidase inhibitory and bacteriostatic effects

Naringenin is a natural flavonoid with strong antioxidant and antibacterial properties, but its poor solubility and limited bioavailability severely restrict its broader application. Addressing this challenge is the key motivation of the present study. This study employed ultrasonic-assisted antisolvent precipitation to fabricate naringenin ultrafine crystals, and the optimal parameters were ascertained as presented below: a surfactant concentration of 0.54 %, a solution concentration of 14.20 mg/mL, and a anti-solvent to solvent ratio of 10.71. Under these established conditions, naringenin nanocrystals featuring a minimum average particle size of 290.51 ± 0.73 nm were successfully obtained. The introduction of ultrasound during the crystallization process played a crucial role, as the acoustic cavitation and subsequent microjets greatly enhanced solvent-antisolvent mixing, promoted uniform supersaturation, and facilitated the formation of evenly distributed nuclei. These effects not only reduced the tendency for particle agglomeration but also improved the reproducibility of the precipitation process. The experimental results revealed that the half-maximal inhibitory concentration (IC ₅₀) value of the ultrafine crystals was 2.61 ± 0.22 μM, representing a significant 9.3 enhancement compared to that of the native naringenin powder. In addition, the antibacterial efficacy of the ultrafine crystals against Staphylococcus aureus was investigated. The ultrafine crystal samples exhibited an inhibition zone diameter of 21.69 mm, corresponding to an inhibition rate of 36.15 %, which clearly outperformed the antibacterial activity of native naringenin. Overall, this study not only demonstrates the efficiency of ultrasonic-assisted crystallization in tailoring particle size and bioactivity, but also highlights its potential as a versatile strategy for expanding the applications of natural flavonoids.