Stealth Me.PEG-PLA nanoparticles avoid uptake by the mononuclear phagocytes system

Authors

  • Didier Bazile,

    Corresponding author
    1. Pharmaceutical Sciences Department, Rhône-Poulenc Rorer, Institut de Biopharmacie, 20 avenue Raymond, Aron 92160, Antony Cedex, France
    2. Pharmacotechny Department, Rhône-Poulenc Rorer, Institut de Biopharmacie, 20 avenue Raymond, Aron 92160, Antony Cedex, France
    • Pharmaceutical Sciences Department, Rhône-Poulenc Rorer, Institut de Biopharmacie, 20 avenue Raymond, Aron 92160, Antony Cedex, France
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  • Christian Prud'homme,

    1. Rhône-Poulenc Recherches, Centre de Recherche des Carrières, BP 62 - 69192 Saint-Fons, France
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  • Marie-Theérèse Bassoullet,

    1. Analysis Department, Rhône-Poulenc Rorer, Institut de Biopharmacie, 20 avenue Raymond, Aron 92160, Antony Cedex, France
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  • Michel Marlard,

    1. Biodynamics Department, Rhône-Poulenc Rorer, Institut de Biopharmacie, 20 avenue Raymond, Aron 92160, Antony Cedex, France
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  • Gilles Spenlehauer,

    1. Pharmaceutical Sciences Department, Rhône-Poulenc Rorer, Institut de Biopharmacie, 20 avenue Raymond, Aron 92160, Antony Cedex, France
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  • Michel Veillard

    1. Pharmaceutical Sciences Department, Rhône-Poulenc Rorer, Institut de Biopharmacie, 20 avenue Raymond, Aron 92160, Antony Cedex, France
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Abstract

Nanoparticles were prepared from methoxy poly(ethylene glycol)poly(d,llactic acid) block copolymers (Me.PEG–PLA) or blends of Me.PEG–PLA and PLA by the precipitation–solvent diffusion method. These nanoparticles, labeled by introducing [14C]PLA in the formulation, were shown to be more slowly captured by cultured THP-1 monocytes than F68-coated PLA nanoparticles, in a PEG chain-length-dependent manner. In vivo, the half-life in plasma of the Me.PEG–PLA nanoparticles that were intravenously administered to rats is increased by a factor 180 compared with the F68-coated PLA nanoparticles. This mononuclear phagocytes system avoidance was explained according to a conformation model in which the PEG density at the surface of the particles is a key parameter.

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