*Article* **Encapsulation of Hydrophobic and Low-Soluble Polyphenols into Nanoliposomes by pH-Driven Method: Naringenin and Naringin as Model Compounds**

**Mianhong Chen 1, Ruyi Li 1,\*, Yuanyuan Gao 1, Yeyu Zheng 1, Liangkun Liao 1, Yupo Cao 1, Jihua Li 1 and Wei Zhou 1,2,3,\***


**Abstract:** Naringenin and naringin are a class of hydrophobic polyphenol compounds and both have several biological activities containing antioxidant, anti-inflammatory and anti-tumor properties. Nevertheless, they have low water solubility and bioavailability, which limits their biological activity. In this study, an easy pH-driven method was applied to load naringenin or naringin into nanoliposomes based on the gradual reduction in their water solubility after the pH changed to acidity. Thus, the naringenin or naringin can be embedded into the hydrophobic region within nanoliposomes from the aqueous phase. A series of naringenin/naringin-loaded nanoliposomes with different pH values, lecithin contents and feeding naringenin/naringin concentrations were prepared by microfluidization and a pH-driven method. The naringin-loaded nanoliposome contained some free naringin due to its higher water solubility at lower pH values and had a relatively low encapsulation efficiency. However, the naringenin-loaded nanoliposomes were predominantly nanometric (44.95–104.4 nm), negatively charged (−14.1 to −19.3 mV) and exhibited relatively high encapsulation efficiency (EE = 95.34% for 0.75 mg/mL naringenin within 1% *w/v* lecithin). Additionally, the naringenin-loaded nanoliposomes still maintained good stability during 31 days of storage at 4 ◦C. This study may help to develop novel food-grade colloidal delivery systems and apply them to introducing naringenin or other lipophilic polyphenols into foods, supplements or drugs.

**Keywords:** naringenin; naringin; nanoliposomes; pH-driven; stability
