We studied different methods of preparing α-tocopherol acetate (ATA) nanoparticles, which are to be used in targeting the lungs as aerosols in order to prevent cigarette smoke toxicity. Poly-(lactide) nanoparticles were prepared using nanoprecipitation and solvent evaporation techniques, which produced, respectively, too small and too large nanoparticles to be aerosolized. The emulsification-diffusion method produced 2 months stable nanoparticles with a size between (500-700 nm). Increasing ATA concentration (1-7 mg/mL) induced a decrease in the association rate (97-93%) and in the adsorbed ATA rate (7-4.5%), which was associated with variations of Zeta potentials (−27.5 to −24.3 mV) and decrease in polymeric wall thickness and density.