To develop rapidly biodegradable "stealth" nanoparticles, a physicochemical investigation was done on the formation of PEG-coated poly(isobutyl 2-cyanoacrylate) (PIBCA) nanoparticles. In particular, this study focused on the effect of polymerization conditions on particle size and surface properties, such as charge and hydrophilicity. Among the parameters involved, the pH of the polymerization medium was found to be a key to control the preparation of PEG-coated nanoparticles. Currently, poly(alkylcyanoacrylate) (PACA) nanoparticles are prepared in H2O at pH 2.5, the most appropriate for producing nanoparticles with a mean diameter of 200 nm and an unimodal size distribution. The presence of PEG in the polymerization medium was shown to affect particles formation: only a pH value < 1.5 led to the formation of colloidal nanoparticles, and slight pH variations dramatically affected particle size and PEG association. Polymer chemistry investigations and chemical determination of PEG strongly suggest that PEG associated with nanoparticles was well copolymerized with PIBCA.