To characterize the physicochemical and biological stability of nanodevices suitable for biomedical applications, polylactic acid (PLA) nanoparticles (NPs) of 112 +/- 6 nm and polyhydroxy butyrate (PHB) of 15 +/- 5 nm size were prepared by standardizing the suitable method for each. Morphology of NPs was studied by scanning and transmission electron microscopy and temperature stability by thermogravimetric analysis. Their stability in biological fluids (simulated gastrointestinal and saliva) and tolerance against 0.5 mM NaCl were analyzed. PHB NPs remained stable in all fluids, while after 24 h treatment, the PLA NPs showed the beginning of disintegration with intestinal fluid mimic. In addition to the preparation of polyethylene glycol (PEG) surface-coated NPs, PLA-PEG-PLA triblock copolymer (MW similar to 7,366 Da) was also chemically synthesized and characterized. Cytotoxicity of all forms of nanoparticles was tested by MTT assay and by annexin pi staining.