STEALTH ME.PEG-PLA NANOPARTICLES AVOID UPTAKE BY THE MONONUCLEAR PHAGOCYTES SYSTEM

Nanoparticles were prepared from methoxy poly(ethylene glycol)poly(d,l -lactic acid) block copolymers (Me.PEG-PLA) or blends of Me.PEG-PLA an d PLA by the precipitation-soivent diffusion method. These nanoparticl es, labeled by introducing [C-14]PLA in the formulation, were shown to be more slowly captured by cultured THP-1 monocytes than F68-coated P LA nanoparticles, in a PEG chain-length-dependent manner. In vivo, the half-life in plasma of the Me.PEG-PLA nanoparticles that were intrave nously 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.