Inhalable nanoparticle-based drug delivery system for non-small cell lung cancer therapy: promises and challenges

Lung cancer remains the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. Conventional therapies, including surgery, chemotherapy, and targeted treatments, often show limited efficacy, especially in advanced stages. Pulmonary drug delivery systems (PDDSs) have gained attention as an innovative approach for NSCLC management by enabling direct drug administration to the lungs. This method improves therapeutic outcomes while minimizing systemic side effects. Advances in nanotechnology have further enhanced the potential of inhalable chemotherapy, with nanoparticles offering notable benefits such as improved drug solubility, stability, and protection from premature degradation. Additionally, their small size and modifiable surfaces allow for targeted delivery to tumor cells, increasing treatment efficacy and reducing harm to healthy tissues. This review outlines the formulations used in PDDSs for NSCLC, evaluates suitable inhalation devices, and examines the physicochemical characteristics of nanoparticles critical for pulmonary delivery. It also discusses both passive and active targeting mechanisms and explores current challenges in inhalable nanomedicine. Emphasis is placed on recent innovations in inhalable nanomaterials, providing a comprehensive and current perspective on their application in NSCLC therapy.