Simultaneous pulmonary administration of celecoxib and naringin using a nebulization-friendly nanoemulsion: A device-targeted delivery for treatment of lung cancer.

BACKGROUND: Lung cancer is a principal cause of death worldwide, and its treatment is very challenging. Nebulization offers a promising means of targeting drugs to their site of action in the lung. RESEARCH DESIGN AND METHODS: In the present study, nebulizable oil in water nanoemulsion formulations was co-loaded with naringin/celecoxib and tested for pulmonary administration by different nebulizer types. RESULTS: The translucent appearance of nanoemulsion formulations was revealed, with particle size (75-106 nm), zeta potential (-3.42 to -4.86 mV), and controlled in-vitro release profiles for both drugs. The nanoemulsions showed favorable stability profiles and superior cytotoxicity on A549 lung cancer cells. Aerosolization studies on the selected nanoemulsion formulation revealed its high stability during nebulization, with the generation of an aerosol of small volume median diameter and mass median aerodynamic diameter lower than 5 µm. Moreover, it demonstrated considerable safety and bioaccumulation in lung tissues, in addition to accumulation in the brain, liver, and bones, which are the main organs to which lung cancer metastasizes. CONCLUSIONS: Nanoemulsion proved to be a promising nebulizable system, which paves the way for treatment of pulmonary diseases other than lung cancer.

Nebulizable colloidal nanoparticles co-encapsulating a COX-2 inhibitor and a herbal compound for treatment of lung cancer.

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.