Polyisobutylcyanoacrylate nanocapsules containing an aqueous core as a novel colloidal carrier for the delivery of oligonucleotides

Purpose. The goal of the present paper was to encapsulate oligonucleotides in a new particulate carrier in order to protect them from enzymatic degrad ation. Methods. Nanocapsules with an aqueous core containing oligonucleotides were prepared by interfacial polymerization of isobutylcyanoacrylate in a W/O e mulsion. Ultracentrifugation and re-suspension in water yielded a dispersio n of these containing an aqueous core nanocapsules. Zeta potential measurem ents and quenching of fluorescence of fluorescein-bounded oligonucleotides were used to study the localization of the oligonucleotides. Oligonucleotid e degradation studies were carried out in fetal calf serum. Results. Polydisperse nanocapsules of size ranging from 20 to 400 nm were o btained. Oligonucleotide loading did not significantly influence the zeta p otential, suggesting they were located within the core of the nanocapsules. Fluorescence quenching assays confirmed this localization. When encapsulat ed in the nanocapsules and incubated in the presence of serum, the oligonuc leotides were efficiently protected from degradation by nucleases, whereas oligonucleotides adsorbed onto nanospheres were protected less efficiently. Conclusions, This paper describes, for the first time, a nanotechnology abl e to encapsulate oligonucleotides rather than adsorbing them at the surface of a solid support. Such a formulation has great potential for oligonucleo tide delivery.