关键词:

"> 芹菜素, pH 敏感, 叶酸修饰, 脂质体, 抗肿瘤

Abstract:

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.

Key words:

"> apigenin, pH-sensitive, folic acid-modified, liposomes, anti-tumor