Abstract In nanoparticulate engineering for drug delivery systems, poloxamers tri block copolymers are employed as adsorbing molecules to modify the aggregation state and impart stability to products. The aim was to prepare nanoparticles using poloxamer188 as stabiliser and investigate the mechanism of stabilisation of the prepared particles. Nanoparticles were prepared by solvent diffusion method with poloxamer 188 as stabiliser. Hydrodynamic thickness and zeta potential of the prepared nanoparticles were determined by photon correlation spectroscopy. To study the extent of adsorption of poloxamer onto the prepared nanoparticles, adsorption isotherms were constructed. The adsorbed amount of poloxamer 188 onto the particles was determined by depletion method. Macrophageal uptake study was performed to assess the uptake of the prepared nanoparticles using RAW 264.7 cell lines. Nanoparticles were prepared with slight increase in particle size and in absolute value of zeta potential compared to uncoated particles suggesting that this effect was due to adsorption of poloxamer 188. TEM studies and surface area analysis supported the results obtained from particle size analysis indicating preparation of particles with a thin layer of adsorbed poloxamer 188. Adsorption kinetics modeling suggested that at low concentrations (0.001-0.010g/L), Langmuir monolayer equation fits quite well and at higher concentrations (above 0.010g/L) multilayer adsorption of poloxamer 188 onto the prepared particles occurred. Thus the nanoparticles had multilayer of poloxamer 188 adsorbed onto the non uniform surface of PLGA. Results of macrophageal uptake and liver cell study exhibits adsorbed concentration dependent bypass of RES uptake of nanoparticles. Hence, results substantiate the application of adsorption isotherms for designing nanoparticles possessing potential to exhibit prolonged circulation when administered in vivo.