Modifying glycyrrhetinic acid liposomes with liver-targeting ligand of galactosylated derivative: preparation and evaluations

// Jing Chen 1, * , Yuchao Chen 1, * , Yi Cheng 1 , Youheng Gao 1 , Pinjing Zheng 1 , Chuangnan Li 2 , Yidan Tong 1 , Zhao Li 1 , Wenhui Luo 3 and Zhao Chen 3 1 School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangdong, China 2 The Second School of Clinic Medicine, Guangzhou University of Chinese Medicine, Guangdong, China 3 Guangdong Second Traditional Chinese Medicine Hospital (Guangdong Research Institute of Traditional Chinese Medicine Engineering Technology), Guangdong, China * These authors have equally contributed to this work Correspondence to: Yi Cheng, email: chengyi@gzucm.edu.cn Youheng Gao, email: gaoyouheng@gzucm.edu.cn Keywords: liver-targeting; galactosylated derivative; glycyrrhetinic acid liposomes; liver disease therapeutic Received: May 18, 2017 Accepted: August 26, 2017 Published: October 27, 2017 ABSTRACT In this study, novel glycyrrhetinic acid (GA) liposomes modified with a liver-targeting galactosylated derivative ligand (Gal) were prepared using a film-dispersion method. To characterize the samples, particle size, zeta potential, drug loading, and encapsulation efficiency were performed. Moreover, plasma and tissues were pre-treated by liquid-liquid extraction and analyzed by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results showed that the mean residence times (MRTs) and the area under the curve (AUC) of GA liposomes with Gal (Gal-GA-LP), and GA liposomes (GA-LP) were higher than the GA solution (GA-S) in plasma. The tissue (liver) distribution of Gal-GA-LP was significantly different in contrast to GA-LP. The relative intake rate (Re) of Gal-GA-LP and GA-LP in the liver was 4.752 and 2.196, respectively. The peak concentration ratio (Ce) of Gal-GA-LP and GA-LP in the liver was 2.796 and 1.083, respectively. The targeting efficiency (Te) of Gal-GA-LP and GA-LP in the liver was 48.193% and 34.718%, respectively. Taken together, the results indicate that Gal-GA-LP is an ideal complex for liver-targeting, and has great potential application in the clinical treatment of hepatic diseases. Drug loading and releasing experiments also indicated that most liposomes are spherical structures and have good dispersity under physiologic conditions, which could prolong GA release efficiency in vitro .