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Progress in Inhaled Drug Delivery For Non-small Cell Lung Cancer (NSCLC): A Non-invasive Pathway To Targeted Therapy

Daram A, Prithipaul V, Diorio AM, Kommarajula P, Kunda NK.

Respiratory Drug Delivery 2026. Volume 1, 2026: 3-0.

Abstract:

Non-small cell lung cancer (NSCLC) continues to be a significant therapeutic challenge as conventional intravenous chemotherapy is often associated with substantial systemic toxicity and fails to deliver the drug to the tumor site. NSCLC treatment is shifting away from traditional chemotherapy to tyrosine kinase inhibitors (TKIs), immunotherapies, and other novel treatment options. Over the past 30 years, inhaled therapy has become a relevant approach for the localized treatment of lung cancer, delivering drugs directly to the respiratory tract. Early efforts to adapt chemotherapeutics for aerosol delivery faced clinical barriers, including environmental leakage of cytotoxic aerosols, localized pulmonary toxicity, and rapid biological clearance by mucociliary mechanisms and alveolar macrophages. In recent years, novel nanocarrier-based pulmonary delivery systems have shown strong potential to overcome the challenges with inhaled anti-cancer therapy. Nanocarriers such as liposomes and cubosomes offer promising physicochemical properties, efficient aerosolization, sustained drug release, and enhanced cellular internalization. This article discusses two case studies: (a) immunoliposomes encapsulating Osimertinib (OB), a third-generation tyrosine kinase inhibitor, and (b) repurposed bedaquiline (BQ), an anti-tuberculosis drug, encapsulated in cubosomes and delivered via nebulization for NSCLC treatment. Both approaches showed enhanced cellular uptake and anti-cancer effects in 2D and 3D cell culture studies. These findings validate the emerging paradigm that inhaled targeted therapy using advanced nanocarrier systems represents a novel next-generation strategy to achieve greater local therapeutic efficacy in NSCLC while minimizing systemic toxicity.