The purpose of the study was to compare and select optimum method for nanoparticles formulation in lung cancer therapeutics. For this experiment etoposide, anti-neoplastic agent was used as study molecule. The nanoparticles were prepared by methods like quassi emulsification solvent diffusion, high speed homogenization, probe sonication, magnetic stirring and compared. The batches for each method were prepared in different ratios of drug to polymers. All the formulated batches were evaluated for %EE, %DL, Particle size, polydispersity index and zeta potential. The method with better results was selected for further factorial model study. The batch with better results from 3² factorial model was investigated further for FTIR, DSC, XRD and drug release study. After comparing results of all the methods, method probe sonication with batch code C8 was found better. After applying factorial model, method with batch code F6 shown better results and showed no interactions between drug and polymer. % Drug release study showed almost two folds increased release. The probe sonication method was optimum method among all the methods. These formulated nanoparticles further can be incorporated in drug delivery for more efficient formulation in treatment of lung cancer.