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

Abstract

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. 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. The translucent appearance of nanoemulsion formulations was revealed, with particle size (75-106 nm), zeta potential (-3.42 to -4.86 mV), and controlled 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. Nanoemulsion proved to be a promising nebulizable system, which paves the way for treatment of pulmonary diseases other than lung cancer.