Nanocarrier-based Strategies: Advancing the Future of Pulmonary DrugDelivery

Abstract: Pulmonary diseases such as lung cancer, cystic fibrosis, asthma, and chronic obstructive pulmonary disease (COPD) are chronic conditions that remain significant global health burdens due to their high prevalence and suboptimal treatment outcomes. Conventional systemic therapies often result in limited drug accumulation at the site of disease and increased risk of systemic side effects. Site-specific mucosal drug delivery to the lungs has emerged as a promising strategy to enhance therapeutic efficacy by ensuring localized drug action and reducing systemic exposure. However, the complex anatomical and physiological barriers of the respiratory tract, i.e., the mucus layer, mucociliary clearance, epithelial tight junctions, and immune defences, pose significant challenges to effective drug delivery and absorption. The study aims to investigate site-specific mucosal drug delivery systems for pulmonary diseases, focusing on nanocarrier-based strategies. It explores physiological and biological barriers in the respiratory tract, recent advances in liposomes, polymeric and solid lipid nanoparticles, functionalization approaches, and integration with inhalation technologies to enhance targeting, bioavailability, and therapeutic outcomes. A comprehensive review of published literature retrieved from scientific databases such as Elsevier, PubMed, and Google Scholar. Relevant preclinical and clinical studies focusing on nanotechnology-based mucosal drug delivery for pulmonary diseases were selected. Emphasis was placed on articles discussing nanocarrier design, targeting strategies, bioavailability, and therapeutic outcomes. Nanocarriers demonstrate significant potential in enhancing mucosal drug delivery through improved adherence, penetration, and controlled release. Functionalization with disease-specific ligands or stimuli-responsive elements further increases their therapeutic precision. Liposomes and polymeric nanoparticles, in particular, show high biocompatibility and tunability. Despite promising outcomes in animal models, clinical translation remains limited due to scalability, regulatory hurdles, and variability in patient-specific lung pathophysiology. Integration of pulmonary science with nanoscale engineering is progressively enabling more accurate inhalation therapies, yet more research is required to bridge the gap between laboratory innovation and clinical application. Site-specific mucosal drug delivery, powered by nanotechnology, offers a transformative approach to the treatment of pulmonary disorders. Continued progress in understanding lung physiology, optimizing nanocarrier design, and refining delivery technologies is essential to overcoming current limitations. These innovations hold the potential to significantly improve therapeutic outcomes and quality of life for patients suffering from chronic pulmonary diseases. Despite promising therapeutic potential, nanotechnology-based pulmonary delivery faces hurdles in clinical validation, safety evaluation, and large-scale production. Addressing these through standardized methods, AI-based optimization, and integration with smart inhalers may advance personalized, safe, and efficient respiratory drug delivery systems.