Antisense oligonucleotide delivery with polyhexylcyanoacrylate nanoparticles as carriers

Polyalkylcyanoacrylate nanoparticles are effective colloidal drug carriers and were prepared by an emulsion polymerization process. Antisense oligonuc leotides were loaded on the particles by adsorption. A cationic polymer, DE AE-dextran, was incorporated into the particle matrix or a cationic hydroph obic detergent (CTAB) was used to form a lipophilic oligonucleotide ion pai r. Enzymatic digestion of the oligonucleotides was almost quantitatively in hibited by this nanoparticle complex and cellular uptake by different cell lines was significantly enhanced. In vivo the biodistribution of the oligon ucleotide nanoparticle complex resulted in targeting of oligonucleotides to the liver. Improvements in antisense treatments with nanoparticles were de monstrated for tumor therapy as well as for antiviral applications. (C) 199 9 Academic Press.