P. Calvo et al., Long-circulating PEGylated polycyanoacrylate nanoparticles as new drug carrier for brain delivery, PHARM RES, 18(8), 2001, pp. 1157-1166
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,