Preparation and evaluation of liposome-encapsulated codrug LMX

A novel codrug (LMX) consisting of Lamivudine and Ursolic acid has been shown to possess the dual action of anti-hepatitis B virus activity and hepatoprotective effects against acute liver injury in vivo. Because of the limited water solubility of LMX, our aims were to design and optimize a liposomal formulation that could facilitate its in vivo administration, and to estimate the potential of LMX-loaded liposomes as oral or intravenous delivery system. In this work, LMX-loaded liposomes were prepared by the thin film hydration method coupled with sonication. LMX-loaded liposomes showed spherical morphology under transmission electron microscope (TEM) analysis. The mean particle size of liposomes was about 210 nm, and the drug entrapment efficiency was more than 90%. Stability data indicated that lyophilized liposomes were stable for at least 6 months at 4 °C. In vitro drug release profile of LMX-loaded liposomes showed a sustained release profile of LMX and an initial mild burst was observed. The relative bioavailability of LMX-loaded liposomes was 1074.8% compared with LMX suspension after oral administration, and 135.2% relative to 50% alcohol solution after intravenous (i.v.) administration. These results indicated that LMX-loaded liposomes were valued to develop as a practical preparation for oral or i.v. administration.

A novel codrug (LMX) consisting of Lamivudine (LMV) and Ursolic acid (UA) was synthesized, and a liposomal formulation of LMX was designed and optimized to facilitate its in vivo administration.81