Inhaled Nanomedicines for Lung Diseases and Injuries: Pharmacological Advances and Clinical Translation.

Abstract

Respiratory diseases remain major causes of morbidity and mortality; however, inadequate pulmonary drug exposure and systemic toxicity continue to limit treatment efficacy. Inhaled nanomedicines offer opportunities for localized, sustained, and targeted therapy. This review examines how disease biology informs pulmonary delivery design across pulmonary fibrosis, lung cancer, chronic obstructive pulmonary disease, pulmonary infections, and acute lung injury/acute respiratory distress syndrome. It outlines anatomical and biological barriers and compares liposomes, lipid nanoparticles, polymeric and hybrid systems, biomimetic carriers, and stimuli-responsive formulations. Particular attention is given to matching therapeutic cargo and carrier properties to fibroblasts, macrophages, tumor cells, and alveolar type II cells. Emerging approaches include mRNA delivery, siRNA-mediated gene silencing, antisense oligonucleotides, and CRISPR-based editing, alongside alveolar regeneration and biomarker-guided treatment. These strategies are evaluated in relation to their delivery requirements and stage of development. The review also addresses aerosol-device compatibility, manufacturing, repeated-dose safety, regulatory considerations, and clinical outcomes. By connecting delivery mechanisms with disease-specific applications and clinical evidence, this review identifies both therapeutic opportunities and barriers to translation. This integrated perspective can guide the development of inhaled nanomedicines with more reproducible pulmonary delivery, improved treatment efficacy, and acceptable safety.