Pharmacokinetics and biodistribution of oligonucleotide adsorbed onto poly(isobutylcyanoacrylate) nanoparticles after intravenous administration in mice

Purpose. The goal of this study was to evaluate the ability of nanoparticles to be used as a targeted delivery system for oligonucleotides. Methods. Pharmacokinetic and tissue distribution were carried out in mice by measuring the radioactivity associated to the model oligothymidylate P-33-pdT(16) loaded to poly(isobutylcyanoacryrate) (PIBCA) nanoparticles. In addition, we have used a TLC linear analyzer to measure quantitatively on a polyacrylamide gel electrophoresis, the amount of non degraded pdT(16). Results. Organ distribution study has shown that nanoparticles deliver P-33-pdT(16) specifically to the liver reducing its distribution in the kidney and in the bone marrow. Nanoparticles could partially protect pdT(16) against degradation in the plasma and in the liver 5 min after administration, whereas free oligonucleotide was totally degraded at the same time. Conclusions. Nanoparticles protect oligonucleotides in vivo against degradation and deliver them to the liver.