Potential and challenges of natural product inhaled formulations in the treatment of pulmonary diseases.

Natural products hold immense potential for the treatment of complex pulmonary diseases due to their multi-target synergistic advantages; however, their clinical application is often constrained by inherent physicochemical limitations, such as poor aqueous solubility and low bioavailability. While inhalation delivery allows for direct targeting of lesions and reduced systemic toxicity, it faces a "tripartite paradox" involving the trade-off between therapeutic efficacy, bioavailability, and safety (EBS). This article systematically reviews the progress of inhaled natural product-based formulations in six major conditions: lung cancer, pulmonary fibrosis, acute lung injury, pulmonary infections, asthma, chronic obstructive pulmonary disease, and pulmonary arterial hypertension. Furthermore, the logic of "pathology-adapted" carrier design is discussed, summarizing core strategies utilizing lipidic, polymeric, biomimetic, and engineered microparticulate systems to overcome physical and immunological pulmonary barriers. Finally, future directions such as smart microenvironment-responsive systems, computational fluid dynamics (CFD) prediction, and microecological assessment are envisioned, providing a robust theoretical foundation for the development of next-generation precision respiratory drug delivery systems.