Purpose. The goal of the present paper was to encapsulateoligonucleotides in a new particulate carrier in order to protect them fromenzymatic degradation. Methods. Nanocapsules with an aqueous core containingoligonucleotides were prepared by interfacial polymerization ofisobutylcyanoacry late in a W/O emulsion. Ultracentrifugation and re-suspensionin water yielded a dispersion of these containing an aqueous core nanocapsules.Zeta potential measurements and quenching of fluorescence offluorescein-bounded oligonucleotides were used to study the localization ofthe oligonucleotides. Oligonucleotide degradation studies were carriedout in fetal calf serum. Results. Polydisperse nanocapsules of size ranging from 20 to 400 nmwere obtained. Oligonucleotide loading did not significantly influencethe zeta potential, suggesting they were located within the core of thenanocapsules. Fluorescence quenching assays confirmed thislocalization. When encapsulated in the nanocapsules and incubated in thepresence of serum, the oligonucleotides were efficiently protected fromdegradation by nucleases, whereas oligonucleotides adsorbed ontonanospheres were protected less efficiently. Conclusions. This paper describes, for the first time, ananotechnologyable to encapsulate oligonucleotides rather than adsorbing them at thesurface of a solid support. Such a formulation has great potential foroligonucleotide delivery.