AbstractIn this research, a novel polymer cholesterol‐poly(ethylene glycol) 2000‐glycyrrhetinic acid (Chol‐PEG‐GA) was synthesized with four steps of chemical modification and elucidated by FTIR and 1H‐NMR spectra. To demonstrate the application of this Chol‐PEG‐GA in preparation of liposomes (CPGL), conventional liposome (CL) composed of PC and Chol was prepared and the effects of the quantity of Chol‐PEG‐GA on the physicochemical properties (entrapment efficiency, particle size, stability of storage, and so on) of CPGL were also evaluated. The ability of the sustained release and the liver targeting ability of CPGL were further studied in vivo in rats and mice. The results show that, the AUC and MRT of CPGL were increased 2.31 and 2.11 times when compared with CL, respectively. The CPGL delivered about seven times higher drug into liver as compared with CL. From the targeting parameters of CPGL and CL, we can also conclude that the CPGL is able to improve the liver targeting of brucine. All these results suggested that, the Chol‐PEG‐GA modified liposomes were potential as the sustained and liver targeting drug delivery. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011