Nasopulmonary Drug Delivery Systems: Recent Advances and Future Perspectives

Abstract

The management of complex respiratory and systemic disorders continues to pose significant challenges in modern pharmacotherapy. Conventional drug administration routes, particularly oral and intravenous delivery, are often limited by poor bioavailability, extensive first-pass metabolism, systemic adverse effects, and enzymatic degradation. In response to these limitations, nasopulmonary drug delivery has emerged as an innovative, non-invasive, and versatile approach for both localized and systemic therapy. This review provides a comprehensive overview of the anatomical, physiological, and formulation-related principles governing effective drug deposition and absorption through the nasal cavity and deep pulmonary regions. The integration of nasal and pulmonary delivery pathways offers important therapeutic advantages. Nasal administration enables rapid local treatment of upper respiratory disorders and provides an alternative route for systemic absorption, while pulmonary delivery facilitates targeted therapy for diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, pulmonary hypertension, and lung cancer. The extensive vascularization, large surface area, and thin alveolar membrane further support rapid systemic absorption of therapeutic agents. The review critically examines major biological barriers that restrict the efficiency of inhalation-based therapies, including mucociliary clearance, enzymatic degradation, limited epithelial permeability, and phagocytic activity of alveolar macrophages. Recent advances in pharmaceutical formulation technologies are also discussed, with particular emphasis on polymeric nanoparticles, liposomes, solid lipid nanoparticles, nanoemulsions, and dry powder inhaler systems. These advanced formulations are designed to improve drug stability, prolong mucosal residence, enhance membrane permeation, and reduce biological clearance. Furthermore, the importance of particle engineering is highlighted, particularly the optimization of aerodynamic diameter, surface charge, morphology, and surface modification to achieve reproducible and site-specific deposition. Modern delivery devices, including pressurized metered-dose inhalers, nebulizers, and advanced nasal spray systems, are also evaluated for their role in improving therapeutic performance and patient compliance. Finally, the review addresses regulatory considerations, industrial scale-up challenges, and the toxicological safety of novel polymeric and lipid-based excipients. Overall, nasopulmonary drug delivery represents a promising platform for the targeted administration of conventional drugs and complex biopharmaceuticals, including peptides, proteins, monoclonal antibodies, and nucleic acid therapeutics. This review provides a holistic perspective on emerging strategies that may facilitate the translation of advanced inhalation technologies from laboratory research to clinically effective and commercially viable therapeutic applications.