Polyalkylcyanoacrylate Nanospheres and Nanocapsules for the Delivery of Antisense Oligonucleotides

Abstract

Active ingredients are being aimed at targets implied in various mechanisms such as nuclear enzymes, receptors, membrane receptors or ionic channels. This non‐specific approach leads to adverse effects. From newly acquired knowledge of the genome, one can now plan to treat diseases by the administration of DNA coding for defective proteins. On the other hand, one can also plan to block expression of harmful proteins such as oncogenic proteins by the use of antisense oligonucleotides. These very short nucleic acids sequences are able to specifically form hybrids with an mRNA and to block the translation of the corresponding protein. However, stability issues and an inability to cross membranes and address suitable cellular compartments still limit the use of oligonucleotides as therapeutic agents. In this review, we focus on nanospheres and nanocapsules made of biodegradable polyisobutylcyanoacrylate polymer for the transport and the targeting of antisense oligonucleotides. Nanospheres are particles on the surface of which the oligonucleotides are adsorbed by ion pair formation using a hydrophobic cation. Nanocapsules are a new type of carrier displaying an aqueous content in which oligonucleotides are dissolved. These two systems both allow protection of oligonucleotides against degradation in the presence of pure serum and lead to in vivo inhibition of tumor growth.