Galactosylated liposomes as oligodeoxynucleotides carrier for hepatocyte-selective targeting.

18mer oligodeoxynucleotides (ODNs) which can inhibit survivin gene expression were selected as a model gene drug. The glycolipid (5-cholestan-3beta-yl)-1-[2-(lactobionyl amido) ethylamido] formate (CHE-LA) which specific target to the cells expressing galactose receptors was synthesized through the reaction of lactone of lactobiono-1,5-lactone (LA) and the amino-group of 2-(cholesteryloxycarbonylamino) ethylamine (CHE). The galactosylated liposome incorporated with CHE-LA containing oligodeoxynucleotides was prepared with SPC, cholesterol, CHE-LA and oligodeoxynucleotides by the thin-film hydration method. 1,1'-Dioctadecyl-3,3,3',3'tetramethylindocarbocyanine perchlorate (Dil) was used as a marker for all the liposome preparations. Compared with conventional liposomes (CL), the galactosylated liposomes (GL) exhibited a drastically increased distribution to the liver in vivo and the galactosylated liposomes containing oligodeoxynucleotides (GLO) can also more efficiently induced an apoptosis of HepG2 cells in vitro than the conventional liposome containing oligodeoxynucleotides (CLO). In addition, the GLO represented an improving of the ODNs entrapment efficiency.