PHARMACOKINETICS AND BIODISTRIBUTION OF OLIGONUCLEOTIDE ADSORBED ONTOPOLY(ISOBUTYLCYANOACRYLATE) NANOPARTICLES AFTER INTRAVENOUS ADMINISTRATION IN MICE

Purpose. The goal of this study was to evaluate the ability of nanopar ticles to be used as a targeted delivery system for oligonucleotides. Methods. Pharmacokinetic and tissue distribution were carried out in m ice by measuring the radioactivity associated to the model oligothymid ylate P-33-pdT(16) loaded to poly(isobutylcyanoacryrate) (PIBCA) nanop articles. In addition, we have used a TLC linear analyzer to measure q uantitatively on a polyacrylamide gel electrophoresis, the amount of n on 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 c ould partially protect pdT(16) against degradation in the plasma and i n the liver 5 min after administration, whereas free oligonucleotide w as totally degraded at the same time. Conclusions. Nanoparticles prote ct oligonucleotides in vivo against degradation and deliver them to th e liver.