Pulmonary inhaled drug delivery systems: From bench to bedside

Pulmonary inhaled drug delivery systems (PIDDSs) have emerged as a transformative approach to treating respiratory diseases and administering systemic drugs. This delivery platform, encompassing inhalation devices and preparations, has garnered global attention due to its non-invasive nature, rapid absorption rates and avoidance of hepatic first-pass effects. Nevertheless, the performance of PIDDSs is significantly affected by patients' breathing patterns and the aerodynamic properties of preparations. The respiratory system's complex physiology and inherent delivery barriers also pose substantial challenges to pulmonary drug delivery, including high administration doses, low pulmonary deposition efficiency, inadequate pulmonary retention and poor patient adherence. In recent years, significant efforts have been devoted to improving inhalation devices minimizing the dependence on patients' breathing patterns. Concurrently, researchers have explored how formulation design impacts the safety, delivery dose, pulmonary retention, and sustained/controlled release properties of inhalation preparations. This review provides a comprehensive analysis of the characteristics of PIDDSs, the in-depth mechanisms of pulmonary deposition and clearance, and recent advancements in optimizing inhalation devices and innovating inhalation preparations. Furthermore, we thoroughly discuss the potential advantages of novel inhalation devices and preparations, as well as the emerging fields of inhaled biologics, and propose future technical directions for PIDDS development.