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 were prepared by using the reverse phase evaporation or the freeze-thawing methodology. They were characterized for oligonucleotide entrapment efficiency, size, oligonucleotide release at different pH and stability. Optimisation of the encapsulation efficiency was carried out by increasing both lipid and antisense oligonucleotide concentrations. Furthermore, adsorption of antisense oligonucleotides onto the liposome surface was investigated by measuring the amount of oligonucleotide adsorbed and the zeta potential of the vesicles. Antisense oligonucleotides were shown to be encapsulated rather than adsorbed onto the vesicle surface. pH-Sensitive liposomes containing the anti-env oligonucleotide were found to inhibit viral spread at low concentrations in infected Dunni cells model. (C) 1997 Elsevier Science B.V.