The lung (surfing) dealer: pulmonary surfactant and drug delivery

The pulmonary route is an attractive route for drug delivery due to its large surface area, extensive vascularization, and avoidance of hepatic first-pass metabolism. Nevertheless, reaching alveolar regions typically requires a complex balance of aerodynamic particle size, airway geometry, patient cooperation and ventilatory capacity.

Research during two decades has pursued the potential use of pulmonary surfactant, the lipid-protein complex that lines and stabilizes the respiratory air-liquid interface, as drug delivery agent. Lung surfactant may incorporate and solubilize hydrophobic drugs, which could then be delivered into the airways as part of surfactant-based liposomes or nanoparticles. In this review, we summarize recent advances as they have reframed the air-lung lining fluid interface to open the innovative concept of interfacial delivery: drugs could actively spread over the respiratory surface, driven by interfacial forces such as those defining pulmonary surfactant action. Literature included in this review was systematically searched in PubMed, Scopus and Google Scholar using targeted keyword combinations.

Key knowledge gaps and technological challenges are identified whose investigation will contribute to develop the full potential of PS-based inhalation delivery strategies.