Long-circulating PEGylated polycyanoacrylate nanoparticles as new drug carrier for brain delivery.
OBJECTIVE
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.
Calvo
P
P
Université  Paris-Sud XI, UMR CNRS 8612, Physico-Chimie, Pharmacotechnie, Biopharmacie, Châtenay-Malabry, France.
Gouritin
B
B
Chacun
H
H
Desmaële
D
D
D'Angelo
J
J
Noel
J P
JP
Georgin
D
D
Fattal
E
E
Andreux
J P
JP
Couvreur
P
P
D000180:Acrylic Resins / Q000493:pharmacokinetics*; D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004058:Diffusion; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D008863:Microspheres; D010316:Particle Size; D010539:Permeability / Q000187:drug effects; D011092:Polyethylene Glycols / Q000493:pharmacokinetics*; D051381:Rats; D013395:Sucrose / Q000008:administration & dosage / Q000493:pharmacokinetics; D013501:Surface-Active Agents / Q000494:pharmacology; D013535:Suspensions; D014018:Tissue Distribution
D000180:Acrylic Resins; D004337:Drug Carriers; D005456:Fluorescent Dyes; D013501:Surface-Active Agents; D013535:Suspensions; D011092:Polyethylene Glycols; D013395:Sucrose