Novel nano-encapsulated limonene: Utilization of drug-in-cyclodextrin-in-liposome formulation to improve the stability and enhance the antioxidant activity

Drug-in-cyclodextrin-in-liposome (DCL) combines advantages of cyclodextrin and liposome. Here, DCL formulation was successfully prepared to encapsulate limonene (Lim), whose characterization revealed that particle size was 147.5 ± 1.3 nm and zeta potential was −48.7 ± 0.8 mV. And the complexation mechanism of Lim/HP-β-CD inclusion complex (the intermediate of DCL) was analyzed by molecular dynamics simulation, showing that Lim was entrapped into the cavity of HP-β-CD through electrostatic and hydrophobic interaction with a molar ratio of 1:1. Notably, DCL formulation not only reduced Lim volatilization in 25℃, but also enhanced the free radical (DPPH· and ABTS·+) scavenging ability of Lim. In summary, Lim-DCL formulation improved the stability and enhanced the antioxidant activity of Lim. DCL nanocarrier system is suitable to preserve volatile and hydrophobic compounds, enlarging their application in pharmaceutics industries.