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A challenging disease such as lung cancer requires the combination of different modalities to achieve beneficial therapeutic outcomes. In this work, PLGA nanoparticles were chosen as colloidal carrier for two drugs with reported anti-lung cancer activity: naringin and celecoxib. PLGA nanoparticles were prepared and characterized for their particle size, zeta potential, entrapment efficiency, in vitro release, stability, morphology, cytotoxicity, as well as aerosolization and nebulization behaviors. Their biodistribution pattern upon pulmonary aerosolization, and safety on healthy lung tissues were determined as well. Results showed that the described system displayed a particle size <260nm with unimodal distribution, entrapment efficiency for celecoxib and naringin reaching 96% and 62% respectively and a controlled release profile for the two drugs. The selected formula displayed favorable nebulization properties with high drug deposition percentages in lower impinger and impactor stages. It also exhibited higher cytotoxic activity on A549 lung cancer cell lines compared to the free drugs combination, while displaying considerable safety on healthy lung tissues. Biodistribution studies delineated the lung deposition potential of the nanoparticles accompanied with high distribution to the bones, brain and liver which are common metastatic sites of lung cancer, proving their promising nature in the treatment of lung cancer., (Copyright © 2016 Elsevier B.V. All rights reserved.)