Nanoparticulate systems for the delivery of antisense oligonucleotides

Antisense oligonucleotides are molecules that are able to inhibit gene expr ession being therefore potentially active for the treatment of viral infect ions or cancer, However, because of their poor stability in biological medi um and their weak intracellular penetration, colloidal drugs carriers such as nanoparticles were developed for the delivery of oligonucleotides (ODN). ODN associated to nanoparticles were shown to be protected against degrada tion and to penetrate more easily into different types of cells. As a conse quence, nanoparticles were shown to improve the efficiency of ODNs for the inhibition of the proliferation of cells expressing the point mutated Ha-ra s gene. In vivo, polyalkylcyanoacrylate (PACA) nanoparticles were able to e fficiently distribute the ODNs to the liver whereas the alginate nanosponge s could concentrate the ODNs in the lungs. Finally, ODN loaded to PACA nano particles were able to improve in mice, the treatment of RAS cells expressi ng the point mutated Ha-ras gene, (C) 2001 Elsevier Science B.V. All rights reserved.