Preparation of pH-sensitive/folic acid-modified apigenin liposomes and its in vivo anti-tumor effect

This study aims to construct pH-sensitive/folic acid-modified apigenin liposomes (pH/FA-Api-Lips), and to conduct pharmacokinetics, tissue distribution and in vivo anti-tumor evaluation. pH/FA-Api-Lips were prepared by film-hydration method, and its physicochemical properties were characterized. Drug release behavior of pH/FA-Api-Lips in phosphate buffer saline solution with different pH values was investigated. HepG2 cells were used to establish the hepatoma-bearing mice model, apigenin and pH/FA-Api-Lips were intravenously injected to the hepatoma-bearing mice at dose of 20 mg/kg. The pharmacokinetics, tissue distribution and anti-tumor effects of pH/FA-Api-Lips in vivo were also investigated. The results showed that average envelopment efficiency, drug loading, particle size and Zeta potential were 92.26% ± 1.72%, 7.49% ± 0.18%, 212.69 ± 7.07 nm and – 21.27 ± 0.59 mV, respectively. The appearance of pH/FA-Api-Lips was vesicular, and the in vitro drug release exhibited obvious pH-sensitivity. pH/FA-Api-Lips enhanced the bioavailability of apigenin, the relative uptake efficiency and peak concentration ratio of apigenin in tumor tissue was increased by 2.64-fold and 1.82-fold, respectively. The results of the pharmacological experiments in vivo showed that pH/FA-Api-Lips significantly inhibited the tumor volume growth in hepatoma-bearing mice, and there was no significant decrease in body weight. pH/FA-Api-Lips increased the tumor inhibition rate of apigenin from 26.76% to 66.67%. Therefore, pH/FA-Api-Lips improved the tumor targeting of apigenin in vivo, and enhanced the anti-tumor efficacy. pH/FA-Api-Lips had the potential to be developed into an anti-tumor drug.