When nanoparticles are injected into the blood for drug delivery or drug detoxification, detrimental interaction of these particles with blood constituents must be avoided. In previous studies, the adsorption of albumin immunoglobulin G, and fibrinogen from blood plasma to a model hydrophobic polymer like polystyrene was investigated as was decreasing surface hydrophobicity, which quantitatively leads to decreasing amounts of adsorbed proteins on latex particles. However, the uptake of other blood constituents, such as inorganic blood electrolytes, by particles and the dispersion/coagulation characteristics of these particles in the blood stream have not been fully studied. Most importantly, the effect s of these particles on blood coagulation and hemolysis are not well known. In the present study, the poly(lactide-co-glycolide) acid(PLGA) nanoparticles were synthesized by using nanoprecipitation. The uptake of blood electrolytes from simulated blood fluid (SBF) and the stability (dispersion/aggregation) of nanoparticles in SBF was examined by using different loading amounts of PLGA and different contact time between PLGA nanoparticles and SBF. The interaction of particles with the organic components of blood was also studied by using the measurement of red blood cell hemolysis and blood clotting with raw PLGA, surfactant modified PLGA, and PEGylated PLGA.