The Pluronic/poly(ethylene glycol) composite nanoparticles (NPs) composed of Pluronic F-68, liquid poly(ethylene glycol) (PEG; molecular weight, 400) and human growth hormone (hGH) were stabilized with the vesicle fusion. When hGH-loaded Pluronic/PEG composite NPs were mixed with vesicles in the aqueous medium, hGH-loaded Pluronic/PEG composite NPs were incorporated into vesicles to form multi-core vesicle NPs. The morphology and size distribution of multi-core vesicle NPs were observed using field emission scanning electron microscopy, cryo-transmission electron microscopy, and a particle size analyzer. When multi-core vesicle NPs were applied as a delivery system for the protein drug, a sustained release pattern of hGH was observed.