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

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.