Development and Characterization of Celecoxib-Loaded Soluplus/Zein Composite Nanoparticles Coated with Chitosan for Pulmonary Drug Delivery.

Non-small cell lung cancer (NSCLC), the most common subtype of lung cancer, remains a major contributor to cancer-related mortality worldwide. Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has beenrepurposed as an anticancer agent for NSCLC therapy. In the present study, celecoxib-loaded Soluplus/zein composite nanoparticles coated with chitosan were successfully developed and evaluated as a promising pulmonary drug delivery system for NSCLC. The nanoparticles were prepared using an antisolvent precipitation technique and demonstrated favorable physicochemical properties. The optimized formulation exhibited a particle size of approximately 190 nm with high encapsulation efficiency (85.34%), and high drug-loading capacity (14.21%). The chitosan coating increased the zeta potential to nearly +30.42 mV, yielding enhanced stability and desirable mucoadhesive properties for pulmonary administration. In vitro release studies revealed sustained release under simulated physiological lung conditions, following diffusion- and swelling-controlled release mechanisms. Cytotoxicity evaluation using the MTT assay demonstrated significant anticancer activity against A549 lung cancer cells while maintaining good biocompatibility toward BEAS-2B normal human bronchial epithelial cells. The optimized nanoparticles also showed efficient transport across an air-liquid interface (ALI) airway epithelial barrier, with a P app value of 4.15 × 10-4 cm·s-1 and 0.38% translocation after 24 h. Furthermore, aerosolized nanoparticles displayed excellent aerodynamic performance, with a fine particle fraction (FPF) of 68.51% and a mass median aerodynamic diameter (MMAD) of 3.93 μm using the Next Generation Impactor (NGI). Overall, these findings highlight the potential of celecoxib-loaded Soluplus/zein nanoparticles coated with chitosan as a promising pulmonary drug delivery system for NSCLC via nebulization.