Long-circulating PEGylated polycyanoacrylate nanoparticles as new drug carrier for brain delivery

Purpose. The aim of this study was to evaluate the ability of long-circulat ing PEGylated cyanoacrylate nanoparticles to diffuse into the brain tissue. Methods. Biodistribution profiles and brain concentrations of [C-14]-radiol abeled PEG-PHDCA, polysorbate 80 or poloxamine 908-coated PHDCA nanoparticl es, and uncoated PHDCA nanoparticles were determined by radioactivity count ing after intravenous administration in mice and rats. In addition, the int egrity of the blood-brain barrier (BBB) after nanoparticles administration was evaluated by in vivo quantification or the diffusion of [C-14]-sucrose into the brain. The location of fluorescent nanoparticles in the brain was also investigated by epi-fluorescent microscopy. Results. Based on their long-circulating characteristics, PEGylated PHDCA n anoparticles penetrated into the brain to a larger extent than all the othe r tested formulations. Particles were localized in the ependymal cells of t he choroid plexuses, in the epithelial cells of pia mater and ventricles, a nd to a lower extent in the capillary endothelial cells of BBB. These pheno mena occurred without any modification of BBB permeability whereas polysorb ate 80-coated nanoparticles owed, in part, their efficacy to BBB permeabili zation induced by the surfactant. Poloxamine 908-coated nanoparticles faile d to increase brain concentration probably because of their inability to in teract with cells. Conclusions. This study proposes PEGylated poly (cyanoacrylate) nanoparticl es as a new brain delivery system and highlights two requirements to design adequate delivery systems for such a purpose: a) long-circulating properti es of the carrier, and b) appropriate surface characteristics to allow inte ractions with BBB endothelial cells,