Liposomal Amodiaquine for Localized Therapy of Non-Small Cell Lung Cancer (NSCLC).

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases and remains associated with a poor five-year overall survival rate (~ 17.4%). Current therapies are limited by suboptimal efficacy and safety, underscoring the need for novel interventions. This study investigates the repurposing of amodiaquine (AQ), an anti-malarial drug, formulated into inhalable liposomes for targeted NSCLC therapy. The AQ-loaded liposomes exhibited favorable physicochemical properties, including sub-200 nm particle size, low polydispersity index (< 0.3), high drug loading (≈40%), and stability for over two months. In-vitro aerosolization studies demonstrated efficient lung-targeting potential, with > 70% of particles depositing in the deep lung regions. Cytotoxicity assays revealed significantly enhanced anticancer potency of AQ-liposomes compared to the free drug in NSCLC cell lines. Furthermore, clonogenic and wound healing assays showed a marked reduction in cancer cell proliferation and migration. Mechanistically, caspase assays indicated elevated apoptosis in AQ-liposome-treated cells. In 3D spheroid models, AQ-liposomes disrupted spheroid integrity more effectively than AQ alone, confirmed by live/dead staining. Collectively, these findings support the potential of inhalable AQ liposomes as a promising therapeutic strategy for NSCLC. Future in vivo studies and clinical evaluation are warranted to validate translational feasibility and therapeutic efficacy in NSCLC management.