Nanodrug Delivery Systems for Lower Respiratory Infections: Pulmonary Targeting, Anti-Infective Applications, and Translational Challenges.

Lower respiratory infections (LRIs) remain a leading cause of global morbidity and mortality, particularly among vulnerable populations such as children and the elderly. Although conventional antimicrobial therapies remain central to clinical management, their efficacy is often limited by poor pulmonary bioavailability, systemic toxicity, inadequate penetration of mucus or biofilms, and the rapid emergence of drug-resistant pathogens. Nanodrug delivery systems (NDDS) provide a promising strategy to address these limitations by improving pulmonary deposition, protecting labile therapeutics, enabling controlled release, and supporting disease-site targeting. In this review, we systematically summarize recent advances in NDDS for LRIs, with emphasis on the design principles and functional characteristics of lipid-based, polymeric, inorganic, and hybrid nanocarriers. We further connect these platforms with disease-specific therapeutic challenges in bacterial pneumonia, tuberculosis, viral infections, and fungal pneumonia, highlighting how carrier composition, surface engineering, and release behavior can be adapted to mucus barriers, biofilms, intracellular pathogen niches, and inflammatory microenvironments. Importantly, we discuss emerging trends, including bioinspired nanocarriers, stimuli-responsive systems, and multifunctional theranostic platforms, while also evaluating key translational barriers such as biosafety, immunogenicity, reproducible manufacturing, and regulatory standardization.