Pulmonary delivery of monoclonal antibodies: challenges, limitations,and modern formulation strategies.

Abstract

Biopharmaceuticals, particularly monoclonal antibodies, represent a key therapeutic class in modern pharmacotherapy for the treatment of autoimmune, inflammatory, oncological, and rare diseases. Despite their high efficacy and specificity, their clinical use is largely limited to parenteral administration, which may negatively affect patient comfort and long-term treatment adherence. In recent years, the inhalation route of administration has emerged as a promising, non-invasive alternative, especially for respiratory diseases. This is due to the large absorptive surface area of the lungs, their rich vascularization, and the possibility of achieving high local drug concentrations while minimizing systemic adverse effects. This review summarizes and critically evaluates current knowledge and emerging trends in the field of inhaled monoclonal antibodies. The text focuses on the specific features of pulmonary physiology, as well as the anatomical, physiological, and immunological barriers influencing the deposition, stability, and absorption of biological therapeutics. Particular attention is given to advanced formulation strategies aimed at improving pulmonary retention and the systemic bioavailability of protein-based drugs. Inhaled administration of biologics may significantly expand the therapeutic potential of monoclonal antibodies in the future and contribute to more effective and targeted treatment strategies.