(3), 504.
Respiratory diseases continue to pose a major global health burden, requiring effective therapeutic strategies. Although oral and injectable routes are widely used for managing these conditions, they suffer from drawbacks such as poor drug targeting to the lungs, susceptibility to first-pass metabolism, and undesirable systemic side effects. Injectable therapies may also result in pain at the administration site, negatively impacting patient adherence. In contrast, pulmonary drug delivery offers direct targeting of the lungs, bypasses hepatic metabolism, reduces systemic toxicity, and improves patient comfort. Despite these advantages, the success of pulmonary delivery is often limited by physiological barriers—including mechanical, chemical, and immune-related defenses—that impede drug deposition, absorption, and retention within the lungs. Additionally, rapid metabolic clearance can lead to a short duration of action following inhalation. Polymeric micelles (PMs), which self-assemble from amphiphilic block copolymers, represent a promising nanocarrier system to overcome these obstacles. Their core–shell architecture allows for the encapsulation of poorly soluble drugs, enhances delivery efficiency, and enables controlled or stimuli-responsive drug release. This review critically explores the potential of PMs in pulmonary drug delivery by addressing lung physiology, biological barriers, and the limitations of current delivery systems. It further examines PM classification, preparation techniques, inhalable formulations, and physicochemical characterization. Finally, the review highlights clinical challenges, safety considerations, regulatory perspectives, and recent advancements, providing a detailed outlook on the future of PM-based inhalation therapies.