Liposome delivery of antisense oligonucleotides: adsorption and efflux characteristics of phosphorothioate oligodeoxynucleotides

Abstract

Antisense oligonucleotides have emerged as potential therapeutic agents for the suppression of individual gene expression. In this study we have investigated the potential of using multilamellar liposomes prepared by a freeze and thaw technique (FATMLV) in the delivery of antisense phosphorothioate oligonucleotides (S-oligos). Adsorption (binding) and efflux (release) kinetics of a 5′ end [ 32P]-labelled 14 mer S-oligo with a sequence complementary to the 5′ splice site of the human β-giobin gene (5′ TAC CAA CCT GCC CA 3′) are reported. S-oligos exhibited saturable binding to liposomes with a binding affinity constant of around 0.0063 nM −1. Release of S-oligo from FATMLV liposomes (mean diameter 0.46 ± 0.20 μm) was relatively slow (efflux t 1 2 in the range 6–9 days) compared to that of a marker compound, [ 3H]-D-gluoose (efflux t 1 2 of about 24 h) and followed first order kinetics. Changes in lipid composition had little influence on oligonucleotide efflux rates. These results are discussed in terms of using liposomes for the sustained delivery of antisense oligonucleotides.