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Pharmaceutical Research

, Volume 18, Issue 8, pp 1157–1166 | Cite as

Long-Circulating PEGylated Polycyanoacrylate Nanoparticles as New Drug Carrier for Brain Delivery

  • Pilar Calvo
  • Bruno Gouritin
  • Hélène Chacun
  • Didier Desmaële
  • Jean D'Angelo
  • Jean-Pierre Noel
  • Dominique Georgin
  • Elias Fattal
  • Jean P. Andreux
  • Patrick Couvreur
Article

Abstract

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.

PEGylated nanoparticles brain targeting polysorbate 80 surfactant coating 

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Copyright information

© Plenum Publishing Corporation 2001

Authors and Affiliations

  • Pilar Calvo
    • 1
  • Bruno Gouritin
    • 2
  • Hélène Chacun
    • 1
  • Didier Desmaële
    • 3
  • Jean D'Angelo
    • 3
  • Jean-Pierre Noel
    • 4
  • Dominique Georgin
    • 4
  • Elias Fattal
    • 1
  • Jean P. Andreux
    • 2
  • Patrick Couvreur
    • 5
  1. 1.Physico-Chimie, Pharmacotechnie, BiopharmacieUniversité Paris-Sud XI, UMR CNRS 8612Châtenay-MalabryFrance
  2. 2.Université Paris-Sud XI, UPRES/EA 2706Châtenay-MalabryFrance
  3. 3.Chimie OrganiqueUniversité Paris-Sud XI, URA CNRS 1843Châtenay-MalabryFrance
  4. 4.Service des Molecules Marquées, CEA/Saclay bat, 547Gif sur YvetteFrance
  5. 5.Physico-Chimie, Pharmacotechnie, BiopharmacieUniversité Paris-Sud XI, UMR CNRS 8612Châtenay-MalabryFrance

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