Optimization of Preparation Conditions for Quercetin Nanoliposomes Using Response Surface Methodology and Evaluation of Their Stability

Quercetin is a flavonol compound with excellent biological activities. However, quercetin exhibits poor stability and solubility in water, which limits its application. In this study, quercetin nanoliposomes (QUE-NL-1) were prepared using an ultrasonic thin-film dispersion method, and the preparation conditions were optimized using response surface methodology. The optimal conditions for preparing QUE-NL-1 were as follows: an evaporation temperature of 35 °C, a drug concentration of 0.20 mg/mL, and a lipid bile ratio of 4:1. The encapsulation rate of QUE-NL-1 is (63.73 ± 2.09)%, the average particle size is 134.11 nm, and the average absolute value of the zeta potential is 37.50 and PDI = 0.24. By analyzing the storage temperature, storage time, and leakage rate of QUE-NL-1 in simulated gastrointestinal fluid, it was found that quercetin exhibits good stability after embedding and can achieve sustained release in intestinal juice. In addition, the cytotoxicity of QUE-NL-1 was not significant, and the survival rate of Caco-2 cells was >90% when the concentration range of QUE-NL-1 was 0.1–0.4 mg/mL. This study provides an efficient method for preparing QUE-NL-1 with small particle sizes, good stability, and high safety, which is of great significance for expanding the application range of quercetin.