Pharmacokinetics and biodistribution of oligonucleotide adsorbed onto poly(isobutylcyanoacrylate) nanoparticles after intravenous administration in mice.
OBJECTIVE
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 radioactivity associated to the model oligothymidylate 33P-pdT16 loaded to poly(isobutylcyanoacryate) (PIBCA) nanoparticles. In addition, we have used a TLC linear analyzer to measure quantitatively on a polyacrylamide gel electrophoresis, the amount of non degraded pdT16.


RESULTS
Organ distribution study has shown that nanoparticles deliver 33P-pdT16 specifically to the liver reducing its distribution in the kidney and in the bone marrow. Nanoparticles could partially protect pdT16 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.
Nakada
Y
Y
Pharmaceuticals Research Center, Kanebo, LTD., Osaka, Japan.
Fattal
E
E
Foulquier
M
M
Couvreur
P
P
D000327:Adsorption; D000818:Animals; D003487:Cyanoacrylates / Q000737:chemistry*; D004337:Drug Carriers; D004355:Drug Stability; D004659:Enbucrilate; D005069:Evaluation Studies as Topic; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008863:Microspheres; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D013942:Thymine Nucleotides / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution / Q000502:physiology
D003487:Cyanoacrylates; D004337:Drug Carriers; D011108:Polymers; D013942:Thymine Nucleotides; D004659:Enbucrilate