OBJECTIVETo prepare long-circulating liposome (LCL) for sustained release of nolatrexed dihydrochloride and evaluate the effect of this preparation against the growth of hepatocarcinoma cells in mice.

METHODSThe long-circulating nolatrexed dihydrochloride liposome was prepared by film dispersion-extrusion combined with ammonium sulphate gradient method. Amphipathic polyethylene glycol-distearoyl phosphatidylethanolamine (PEG-DSPE) was added to modify the property of the liposome membrane. The drug entrapment efficiency of the nolatrexed dihydrochloride-containing liposome was determined using UV detector with Sephadex G50. Electron microscopy and laser particle analyzer were employed to determine the size of the nolatrexed dihydrochloride liposome. For in vivo evaluation of the effect of the liposomal preparation, H22 mouse hepatoma carcinoma cells were transplanted subcutaneouly in mice in the axillary region of the right hind limb to induce growth of solid tumors, which were evaluated for tumor weight inhibition rate and tumor volume changes after administration of the LCL preparations.

RESULTSThe mean diameter of the long-circulating nolatrexed dihydrochloride liposomes was 109 nm, with an entrapment efficiency of 68.5%. In vivo antitumor experiment showed that both the common liposomal and LCL preparations of nolatrexed dihydrochloride produced antitumor effect in vivo, and the latter had weaker antitumor effect than free and common liposomal preparation of nolatrexed dihydrochloride, but in the long term, the LCL preparation showed stronger antitumor effect with a tumor weight inhibition rate of 41.68%.

CONCLUSIONLCL allows sustained release of nolatrexed dihydrochloride in vivo, and may effectively lengthen the relatively short half life of this drug after administration.