Enhanced distribution and extended elimination of glycyrrhetinic acid in mice liver by mPEG-PLA modified (mPEGylated) liposome

Abstract

A rapid and simple method of high-performance liquid chromatography with UV detector for the quantification of glycyrrhetinic acid (GA) in mice plasma and tissues has been developed and validated. With the established assay method, the pharmacokinetic profiles and tissue distribution of GA in different formulations are compared in mice after intravenous administration of the drug (25 mg/kg). The results showed that mPEG-PLA modified (mPEGylated) GA liposome (PL-GA) significantly prolonged the mean residence time ( MRT) of GA in mice plasma and liver ( MRT: 0.43 ± 0.13 and 1.72 ± 0.11 h, respectively) than the normal GA liposome (L-GA) ( MRT: 0.23 ± 0.01 and 1.07 ± 0.31 h, respectively) and GA sodium injection (S-GA) ( MRT: 0.13 ± 0.01 and 0.95 ± 0.08 h, respectively). Moreover, PL-GA specifically increased GA uptake in liver ( AUC 0–∞, liver value of 1.6-fold and 1.3-fold higher than that for S-GA and L-GA, respectively) and reduced its distribution into other tissues after dosing. Due to these pharmacokinetic properties, it may be promising to develop PL-GA further as a new pharmaceutical preparation for GA on the treatment of various chronic hepatic diseases.