Nanotechnology-driven targeted pulmonary drug delivery: Innovations, insights, and clinical horizons

Pulmonary drug delivery via inhalation offers rapid onset, high bioavailability, and reduced systemic toxicity, making it a valuable platform for localized therapy. Advances in nanotechnology have further enhanced inhaled therapies by improving drug solubility, stability, and targeted lung deposition. This review highlights recent progress in nanotechnology-based inhalation systems, including liposomes, nanostructured lipid carriers, dendrimers, magnetic nanoparticles, nanocomposites, nanocrystals, and both polymeric and inorganic nanocarriers. Their applications are discussed in in the treatment of respiratory diseases, such as bacterial, and viral infections, as well as in the pulmonary delivery of macromolecules such as siRNA, proteins, and mRNA. Particular emphasis is given to targeted lung therapy through passive and active strategies, and to the development of stimuli-responsive nanocarriers. Emerging clinical applications, including inhalable diagnostic agents, are also addressed. Despite these advances, inhaled nanomedicines face persistent challenges related to formulation stability, large-scale production, long-term toxicity, regulatory requirements, and physiological pulmonary barriers. Unlike previous reviews that focus on either formulation aspects or therapeutic outcomes in isolation, this article provides an integrated perspective, combining nanocarrier innovations with practical challenges of pulmonary delivery, updates from recent clinical trials, and the expanding role of inhalation technology in both therapy and diagnostics.