Pulmonary Drug Delivery for Infectious Diseases: Cutting-Edge Formulations and Manufacturing Technologies.

Abstract

Pulmonary drug delivery has emerged as a powerful strategy for the treatment of respiratory infectious diseases, including bacterial, fungal, and viral infections such as influenza and COVID-19, by enabling high local drug concentrations while minimizing systemic exposure. However, the clinical success of inhaled anti-infective therapies critically depends on the precise engineering of particle properties that govern lung deposition, cellular targeting, and therapeutic efficacy. In this review, we provide a comprehensive and technology-driven overview of cutting-edge formulation and manufacturing strategies for pulmonary drug delivery, with particular emphasis on the key process and formulation parameters required to generate effective inhalable systems for the treatment of infectious diseases. Advanced particle-engineering approaches, including spray drying, spray freeze drying, jet milling, and supercritical fluid technologies are discussed as enabling tools to tightly control aerodynamic particle size, morphology, and solid-state properties. In parallel, emerging platforms such as nanoparticle-based delivery systems are examined for their ability to target specific lung cell populations, including epithelial cells and alveolar macrophages, thereby enhancing antimicrobial efficacy. Finally, innovative manufacturing concepts such as microfluidics and three-dimensional (3D) printing are highlighted as promising strategies to improve particle size uniformity, reproducibility, and formulation customization. By integrating formulation science with advanced manufacturing technologies, this review identifies the critical design and processing parameters that underpin effective pulmonary delivery of anti-infective therapies and outlines future directions for the development of next-generation inhaled treatments.