Polyisobutylcyanoacrylate nanocapsules containing an aqueous core for the delivery of oligonucleotides

Antisense oligonucleotides (ODNs) with base sequences complementary to a sp ecific RNA can, after binding to intracellular mRNA, selectively modulate t he expression of a gene. However, these molecules are poorly stable in biol ogical fluids and are characterized by a low intracellular penetration. In view of using ODNs as active molecules, the development of nanocapsules con taining ODNs in their aqueous core was considered. Nanocapsules were prepar ed by interfacial polymerization of isobutylcyanoacrylate (IBCA) in a W/O e mulsion. After ultracentrifugation and re-suspension in water. the nanocaps ules displayed a size of 350 +/- 100 nm. Oligonucleotide loading did not si gnificantly influence the zeta potential, suggesting that they were located within the core of the nanocapsules. Fluorescence quenching assays confirm ed this localization. When encapsulated in the nanocapsules and incubated i n the presence of serum, the ODNs were efficiently protected from degradati on by nucleases, whereas ODNs adsorbed onto nanospheres were less efficient ly protected. This paper describes, for the first time, a nanotechnology ab le to encapsulate ODNs, rather than adsorbing them at the surface of a soli d support. Such a formulation has great potential for oligonucleotide deliv ery. (C) 2001 Elsevier Science B.V. All rights reserved.