Advanced Pulmonary Drug Delivery Systems: A Narrative Review.

Pulmonary drug delivery systems have gained increasing attention as an effective strategy for the treatment of both respiratory and systemic diseases by enabling targeted, noninvasive, and efficient drug administration through the lungs, with advantages including rapid onset of action, lower drug doses, and reduced systemic adverse effects. Despite these advances, challenges related to formulation stability, aerosol performance, lung clearance mechanisms, and regulatory approval remain. This review explores advanced pulmonary drug delivery systems, with emphasis on the anatomical, physiological, pharmaceutical, and device-related factors that influence aerosol deposition and therapeutic performance. The review examines key mechanisms of particle deposition such as inertial impaction, gravitational sedimentation, Brownian diffusion, interception, and electrostatic interactions, and advanced pulmonary drug carrier systems, including liposomes, nanoparticles, large porous particles, dendrimers, polymeric micelles, biodegradable polymers, and lactose-based dry powder platforms, which enhance drug stability, controlled release, lung retention, and site-specific targeting. The review further summarizes advances in particle engineering technologies and common and advanced inhalation devices, including pressurized metered-dose inhalers, dry powder inhalers, nebulizers, soft mist inhalers, and smart inhaler platforms. Clinical applications of pulmonary drug delivery extend beyond asthma and chronic obstructive pulmonary disease (COPD) to include cystic fibrosis, pulmonary infections, and pulmonary arterial hypertension, while emerging applications in tuberculosis, diabetes, vaccination, gene therapy, and cancer continue to be investigated. Future directions include personalized pulmonary medicine, inhaled biologics and mRNA therapeutics, environmentally sustainable inhaler technologies, artificial intelligence-assisted formulation and device optimization, and evolving regulatory frameworks. Advancements in pulmonary drug delivery technologies may focus on improving drug targeting, optimizing therapeutic performance, and broadening their application in modern clinical practice.