Stealth (R) PEGylated polycyanoacrylate nanoparticles for intravenous administration and splenic targeting

The aim of the present work was to investigate the biodistribution characte ristics of PEG-coated polycyanoacrylate nanoparticles prepared by the nanop recipitation/solvent diffusion method using the previously synthesized poly (MePEGcyanoacrylate-hexadecylcyanoaclylate) copolymer. It was observed that [C-14]-radiolabeled PEGylated nanoparticles remained for a longer time in the blood circulation after intravenous administration to mice, compared to the non-PEGylated poly(hexadecylcyanoacrylate) (PHDCA) nanoparticles. Furt hermore, hepatic accumulation was dramatically reduced, whereas a highly in creased spleen uptake was shown. The PEGylation degree of the polymer seeme d not to affect the in vivo behavior of the nanoparticles, whereas previous ly obtained in vitro data have shown a modification of plasma protein adsor ption depending on the density of PEG at the surface of the particles. More over, the study of the in vitro cytotoxicity of the nanoparticles revealed that the PEGylation of the cyanoacrylate polymer reduced its toxicity. Thes e results open up interesting perspectives for the targeting of drugs to ot her tissues than the Liver. (C) 1999 Elsevier Science B.V. All rights reser ved.