Recent Developments in Aerosol Pulmonary Drug Delivery: New Technologies, New Cargos, and New Targets

Abstract

There is nothing like a global pandemic to motivate the need for improved respiratory treatments and mucosal vaccines. Stimulated by the COVID-19 pandemic, pulmonary aerosol drug delivery has seen a flourish of activity, building on the prior decades of innovation in particle engineering, inhaler device technologies, and clinical understanding. As such, the field has expanded into new directions and is working toward the efficient delivery of increasingly complex cargos to address a wider range of respiratory diseases. This review seeks to highlight recent innovations in approaches to personalize inhalation drug delivery, deliver complex cargos, and diversify the targets treated and prevented through pulmonary drug delivery. We aim to inform readers of the emerging efforts within the field and predict where future breakthroughs are expected to impact the treatment of respiratory diseases.

Keywords: aerosol; inhalation; inhaled biologics; inhaled vaccines; nanoparticle.

Figure 1

Emerging paradigms of pulmonary drug delivery. Enabling innovations of new cargo modalities, particle engineering technologies, device innovations, and appreciation of patient heterogeneity have led to significant advances in the field of pulmonary drug delivery toward a broader range of therapeutic targets impacting the lung. Abbreviations: DPI, dry powder inhaler; MDI, metered dose inhaler; SMI, soft mist inhaler.

Figure 2

(a) Structure of the upper airway of the human lung. Mouth inlet is idealized, while the trachea and bronchi are obtained from a healthy adult male (12). Generations 0–3 (G0–G3) are labeled, and representative generations are indicated for the lobar and segmental bronchi. (b) Diagram depicting the role of aerodynamic diameter (d_ae) in generational deposition within the lung, where ~10-μm aerosols deposit in the oropharynx and trachea, ~5-μm aerosols deposit in the upper conducting airways, and ~1-μm aerosols reach the respiratory airways (6).

Figure 3

(a) Advances in particle engineering include approaches to improve aerosol transport efficiency, including spray drying, micromolding, and excipient enhanced growth (EEG). The use of nanoparticles aims to improve mucosal penetration. Scanning electron micrographs (SEMs) show relative differences of representative formulations from each particle engineering approach. Panel SEM images adapted with permission from References –. (b) Regional targeting attempts to deliver aerosols to a target site within the lung that may require lobe- and generation-specific targeting. Approaches for regional targeting are highlighted and include () controlled release positions of aerosols entering the mouth to follow streamlines toward the target location, () use of external forces such as an applied magnet or gravity to direct responsive aerosols to the target, and () design of active microbots that self-assemble after deposition and swarm toward the target location, often with assistance from an external magnetic force.