Quantification and localization of PEGylated polycyanoacrylate nanoparticles in brain and spinal cord during experimental allergic encephalomyelitis in the rat.
Under healthy conditions, the blood-brain barrier (BBB) limits the passage of solutes and cells from the blood to the CNS. During neurological diseases, BBB permeability increases dramatically and it has been hypothesized that drug carrier systems such as polymeric nanoparticles could cross the BBB and penetrate into the CNS. PEGylated polyalkylcyanoacrylate nanoparticles (long-circulating carrier) are one such system and have been investigated during experimental allergic encephalomyelitis (EAE). Brain and spinal cord concentrations of [(14)C]-radiolabelled PEGylated polyalkylcyanoacrylate nanoparticles were compared with another blood long-circulating carrier (poloxamine 908-coated polyalkylcyanoacrylate nanoparticles) and with conventional non-long-circulating polyalkylcyanoacrylate nanoparticles. The microscopic localization of fluorescent nanoparticles in the CNS was also investigated in order to further understand the mechanism by which the particles penetrate the BBB. The results demonstrate that the concentration of PEGylated nanoparticles in the CNS, especially in white matter, is greatly increased in comparison to conventional non-PEGylated nanoparticles. In addition, this increase was significantly higher in pathological situations where BBB permeability is augmented and/or macrophages have infiltrated. Passive diffusion and macrophage uptake in inflammatory lesions seems to be the mechanism underlying such particles' brain penetration. Based on their long-circulating properties in blood and on their surface characteristics that allow cell interactions, PEGylated nanoparticles penetrated into CNS to a larger extent than all the other formulations tested. Thus, PEGylated polycyanoacrylate nanoparticles are proposed here as a new brain delivery system for neuroinflammatory diseases.
Calvo
Pilar
P
Université Paris-Sud XI, Faculté de Pharmacie, Physico-Chimie-Pharmacotechnie-Biopharmacie, UMR CNRS 8612, 5, rue Jean Baptiste Clément, 92296 Châtenay-Malabry, France.
Gouritin
Bruno
B
Villarroya
Henri
H
Eclancher
Françoise
F
Giannavola
Claudia
C
Klein
Christophe
C
Andreux
Jean P
JP
Couvreur
Patrick
P
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002250:Carbon Radioisotopes; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003487:Cyanoacrylates / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005456:Fluorescent Dyes; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D008863:Microspheres; D036103:Nanotechnology / Q000379:methods / Q000639:trends; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011108:Polymers / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D002250:Carbon Radioisotopes; D003487:Cyanoacrylates; D005456:Fluorescent Dyes; D011108:Polymers; D011092:Polyethylene Glycols