More MS news articles for May 2002

Quantification and localization of PEGylated polycyanoacrylate nanoparticles in brain and spinal cord during experimental allergic encephalomyelitis in the rat

Eur J Neurosci 2002 Apr;15(8):1317-1326
Calvo P, Gouritin B, Villarroya H, Eclancher F, Giannavola C, Klein C, Andreux JP, Couvreur P.
Universite Paris-Sud XI, Faculte de Pharmacie, Physico-Chimie-Pharmacotechnie-Biopharmacie, UMR CNRS 8612, 5, rue Jean Baptiste Clement, 92296 Chatenay-Malabry, France Universite Paris-XI, UPRES/EA 2706, 5, rue Jean Baptiste Clement, 92296 Chatenay-Malabry, France Centre Biomedical de Cordeliers, INSERM U450, 15, rue d'Ecole de Medecine, 75270 Paris Cedex 06, France Centre de Neurochimie du CNRS, Laboratoire de Neurobiologie, CNRS UPR 1352, Strasbourg, France Centre Biomedical de Cordeliers, INSERM IFR 58, 15, rue d'Ecole de Medecine, 75270 Paris Cedex 06, France.

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 [14C]-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.