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-circulating PEGylated cyanoacrylate nanoparticles to diffuse into the brain tissue.

METHODS

Biodistribution profiles and brain concentrations of [14C]-radiolabeled PEG-PHDCA, polysorbate 80 or poloxamine 908-coated PHDCA nanoparticles, and uncoated PHDCA nanoparticles were determined by radioactivity counting after intravenous administration in mice and rats. In addition, the integrity of the blood-brain barrier (BBB) after nanoparticles administration was evaluated by in vivo quantification of the diffusion of [14C]-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 nanoparticles penetrated into the brain to a larger extent than all the other tested formulations. Particles were localized in the ependymal cells of the choroid plexuses, in the epithelial cells of pia mater and ventricles, and to a lower extent in the capillary endothelial cells of BBB. These phenomena occurred without any modification of BBB permeability whereas polysorbate 80-coated nanoparticles owed, in part, their efficacy to BBB permeabilization induced by the surfactant. Poloxamine 908-coated nanoparticles failed to increase brain concentration probably because of their inability to interact with cells.

CONCLUSIONS

This study proposes PEGylated poly (cyanoacrylate) nanoparticles as a new brain delivery system and highlights two requirements to design adequate delivery systems for such a purpose: a) long-circulating properties of the carrier, and b) appropriate surface characteristics to allow interactions with BBB endothelial cells.