Journal of Bioactive and Compatible Polymers

 

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Journal of Bioactive and Compatible Polymers, Vol. 23, No. 1, 49-68 (2008)
DOI: 10.1177/0883911507085280
© 2008 SAGE Publications

Synthesis and In vivo Studies of Protein C-loaded Nanoparticles with PEO Modified Surfaces

David Chognot

Laboratoire de Chimie Physique Macromoléculaire, UMR CNRS-INPL 7568 ENSIC, BP 20451, 54001 Nancy Cedex, France

Jean-Luc Six

Laboratoire de Chimie Physique Macromoléculaire, UMR CNRS-INPL 7568 ENSIC, BP 20451, 54001 Nancy Cedex, France

Michèle Léonard

Laboratoire de Chimie Physique Macromoléculaire, UMR CNRS-INPL 7568 ENSIC, BP 20451, 54001 Nancy Cedex, France

Edith Dellacherie

Laboratoire de Chimie Physique Macromoléculaire, UMR CNRS-INPL 7568 ENSIC, BP 20451, 54001 Nancy Cedex, France, edith.dellacherie@ ensic.inpl-nancy.fr

Béatrice Faivre

Mise en forme et évaluation de matériaux d'intérêt thérapeutique et biologique, EA 3452, Faculté de Pharmacie, BP 403, 54001 NANCY Cedex, France

François Bonneaux

Mise en forme et évaluation de matériaux d'intérêt thérapeutique et biologique, EA 3452, Faculté de Pharmacie, BP 403, 54001 NANCY Cedex, France

Claude Vigneron

Mise en forme et évaluation de matériaux d'intérêt thérapeutique et biologique, EA 3452, Faculté de Pharmacie, BP 403, 54001 NANCY Cedex, France

Protein C-loaded nanoparticles coated with monomethoxypoly (ethylene oxide) (MPEO) were prepared by double emulsion/solvent evaporation using water-soluble biocompatible copolymers of MPEO and polylactide, as surfactants of the secondary emulsion. The nanoparticle preparation was optimized to obtain the best yield of encapsulated protein C and provide the greatest retention of its biological activity. The nanoparticles were characterized in terms of size, zeta potential, and thickness of the MPEO external layer. Protein C-loaded nanoparticles were injected into the bloodstream of guinea pigs and the protein concentration in plasma is measured as a function of time. After a rapid release corresponding to 20% of the injected protein, the protein plasma concentration progressively decreased and reached a value close to zero after 5 h. Consequently, the in vivo fate of the fluorescent nanoparticles coated with or without MPEO is studied. The uncoated nanoparticles were rapidly captured by the circulating granulocytes while the coated ones were not. The histological analysis of the spleen, 1 hour after injection, showed that the MPEO-coated particles were retained in this organ, while the uncoated ones were not captured.

Key Words: encapsulation • protein C • MPEO-coated nanoparticles • experiments on guinea pigs • spleen filtration.


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