Inhalable ivermectin-loaded lipid-polymer hybrid nanoparticles as a promising anticancer platform for non-small cell lung cancer.

Abstract

Pulmonary drug delivery offers a compelling strategy for lung diseases including lung cancer, which remains the leading cause of cancer-related mortalities worldwide, by enabling direct tumour site targeting, avoidance of first-pass metabolism, and high local drug concentrations with reduced systemic toxicity. In this study, inhalable ivermectin-loaded lipid-polymer hybrid nanoparticles (IVM-LPHNPs) were investigated in A549 and H460 non-small cell lung cancer cell lines (NSCLC). Cellular uptake was examined by confocal microscopy and flow cytometry, while in vitro therapeutic efficacy was evaluated through cell viability, wound healing, and colony formation assays to determine their anticancer, anti-proliferative, anti-migratory, and anti-clonogenic activities. Cellular uptake analysis confirmed improved intracellular accumulation of coumarin-6 loaded -LPHNPs relative to free coumarin-6. Moreover, IVM-LPHNPs demonstrated approximately 20% reduction in IC50 compared to free ivermectin, while blank LPHNPs did not reduce viability. Developed formulations showed no considerable toxicity to human bronchial epithelial cells, confirming the safety of LPHNPs for healthy lung cells. Furthermore, more than 50% reduction in clonogenic survival and significantly greater inhibition of cell proliferation and migration was observed in IVM-loaded LPHNPs compared to free IVM. Collectively, these findings position IVM-LPHNPs as a promising inhalable platform for the localized treatment of NSCLC, warranting further investigation in preclinical models.

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