Breathing new life nanomedicines for pulmonary drug delivery: targeting approaches, experimental models, and regulatory aspects

Background: The lungs serve a critical function in air transport and gas exchange, presenting an appealing route for noninvasive drug administration. However, the unique physiology and anatomy of the lungs influence the efficacy and safety of pulmonary drug delivery. A comprehensive approach combining both an optimized pharmaceutical formulation and an appropriate delivery device is essential for effective pulmonary therapies. Main body: Pulmonary drug delivery can achieve both local and systemic effects. During pulmonary drug delivery, several factors viz. particle size, electrostatic charge, inhalation parameters, airway functionality, disease state, and proper use of delivery device must be considered. Current advancements in nanotechnology have led to the development of innovative nanocarriers tailored for pulmonary administration. These nanocarriers offer benefits such as targeted deposition in specific areas of the tracheobronchial tree, controlled drug release, protection of active pharmaceutical ingredients (APIs) from lung clearance mechanisms, and cell-specific targeting. Research on nanomedicine for pulmonary delivery has progressed significantly, resulting in the development of several (nano)formulations, devices, and products in various stages of clinical development, with some already commercially available. Recent studies have focused on improving inhalation device testing, aerosol formulation development, and the application of in vitro, ex vivo, in vivo, and in silico models to better understand pulmonary drug deposition and disposition. Conclusion: This review highlights the anatomical and physiological features of the lungs, recent advances in nanocarrier design and inhalation technologies. In addition, the applications in respiratory and systemic disease management have also been included. While significant progress has been made, challenges remain in optimizing pulmonary drug delivery systems, necessitating further research to address these complexities and enhance the therapeutic outcomes.