DELIVERY OF ANTISENSE OLIGONUCLEOTIDES BY MEANS OF PH-SENSITIVE LIPOSOMES

The concept of pa-sensitive liposomes has been applied to the delivery of an oligonucleotide complementary to the AUG region of the env mRNA of the Friend retrovirus. The oligonucleotide-containing liposomes we re prepared by using the reverse phase evaporation or the freeze-thawi ng methodology. They were characterized for oligonucleotide entrapment efficiency, size, oligonucleotide release at different pH and stabili ty. Optimisation of the encapsulation efficiency was carried out by in creasing both lipid and antisense oligonucleotide concentrations. Furt hermore, adsorption of antisense oligonucleotides onto the liposome su rface was investigated by measuring the amount of oligonucleotide adso rbed and the zeta potential of the vesicles. Antisense oligonucleotide s were shown to be encapsulated rather than adsorbed onto the vesicle surface. pH-Sensitive liposomes containing the anti-env oligonucleotid e were found to inhibit viral spread at low concentrations in infected Dunni cells model. (C) 1997 Elsevier Science B.V.