Pulmonary drug delivery has gained renewed attention as an effective strategy for treating both respiratory and systemic diseases by enabling targeted, noninvasive delivery via the lungs. The approach offers advantages such as rapid onset of action, lower administered doses, and reduced systemic adverse events. Despite these benefits, translation into widespread clinical use remains constrained by issues related to formulation stability, aerosol performance, lung clearance mechanisms, and regulatory approval.
This review synthesizes current understanding of the anatomical, physiological, pharmaceutical, and device-related factors that determine aerosol deposition and overall therapeutic performance for inhaled medicines. It also summarizes advanced carrier platforms, particle engineering approaches, inhalation devices, clinical uses, and emerging directions for the field.
Aerosol delivery to the lung is determined by an interplay of factors: the respiratory tract anatomy and regional airflow patterns, the physicochemical properties of particles or droplets, and device performance characteristics. Formulation stability and aerosolization behavior directly affect the dose actually delivered to target lung regions. Lung clearance mechanisms—mucociliary clearance and alveolar macrophage activity—also influence retention time and effective exposure of the lung tissue to the therapeutic agent. Regulatory considerations further shape translation of novel formulations and devices.
Several physical mechanisms govern where and how inhaled particles deposit in the respiratory tract. Key mechanisms described in the source include:
Understanding these processes is critical for designing particles and devices to achieve region-specific delivery and optimize therapeutic effect.
The review highlights multiple carrier platforms developed to improve stability, control release, extend lung retention, and enable targeting. These include:
Each carrier type targets specific formulation goals—improving drug stability during storage and aerosolization, enabling controlled or sustained release, increasing lung retention, and facilitating site-specific delivery.
Advances in particle engineering aim to produce aerosols with predictable aerodynamic properties tailored to deposition targets. Engineering approaches modify particle size, shape, density, porosity, surface charge, and composition to tune deposition and clearance.
The review also describes common and advanced inhaler technologies: pressurized metered-dose inhalers (pMDIs), dry powder inhalers (DPIs), nebulizers, soft mist inhalers, and emerging smart inhaler platforms that integrate electronic monitoring or connectivity. Device selection interacts with formulation design; optimal therapeutic performance requires harmonizing particle properties with the aerosol generation and inhalation mechanics of the chosen device.
Pulmonary delivery continues to be central to management of asthma and chronic obstructive pulmonary disease (COPD). The review notes established and developing applications including cystic fibrosis, pulmonary infections, and pulmonary arterial hypertension. It also highlights research into broader systemic and preventative uses: tuberculosis, diabetes (systemic absorption), vaccination, gene therapy, and cancer are being investigated as potential indications for inhaled therapeutics.
Future priorities identified include personalized pulmonary medicine approaches, development and clinical translation of inhaled biologics and mRNA therapeutics, and innovations in environmentally sustainable inhaler technologies. The review also points to opportunities for artificial intelligence-assisted formulation and device optimization. Concurrently, evolving regulatory frameworks will be important to enable safe, effective, and scalable translation of these technologies to clinical practice.
The authors declared no conflicts of interest. The article is based on previously conducted studies and contains no new studies with human participants or animals performed by the authors.
Advancements in pulmonary drug delivery focus on improving drug targeting, optimizing therapeutic performance, and broadening clinical applications. Continued progress in carrier systems, particle engineering, device technologies, and regulatory pathways will be essential to realize the full potential of inhalation as a route for both respiratory and systemic therapies.