Advancements in Inhalation Technologies for Pulmonary Delivery of Protein Therapeutics.

Inhalation delivery of protein therapeutics has emerged as a promising non-invasive alternative to traditional injectable formulations that offers potential for both localized and systemic treatment of pulmonary diseases. This review comprehensively summarizes the current advances in inhalable protein formulations, with emphasis on design strategies, formulation technologies, barriers to effective delivery, and disease-specific applications. Key aspects include the role of particle size, surface charge, and protein engineering in optimizing lung deposition and cellular uptake, as well as techniques such as spray freeze drying and PEGylation to enhance protein stability. The review also explores novel therapeutic approaches that target cystic fibrosis, asthma, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, lung infections, and cancer, including the use of antibodies, nanobodies, exosomes, and albumin-based carriers. Clinical translation remains limited, but ongoing innovation in delivery systems and molecular design is thought to hold significant promise for expanding the therapeutic landscape of inhaled protein drugs.