Preserving the Surface Activity of Lung Surfactant Using Soft Nebulization

Inhalable aerosols produced by nebulization offer a promising noninvasive route for lung drug delivery. Yet, high shear stresses during nebulization are highly detrimental to many complex biopharmaceuticals, such as lung surfactants, leading to degradation and further reducing their efficacy. Herein, to mitigate this issue, a novel soft nebulization approach with low‐energy input is proposed. Results demonstrate that the lung surfactant aerosolized by soft nebulization undergoes minimal structural alteration and retains its good surface activity in maintaining low surface tension, compared to vibrating mesh nebulization. Upon deposition at the air–liquid interface, the initial spreading of lung surfactant is driven by the Marangoni effect, followed by adsorption and reorganization of lamellar layers. Notably, the lung surfactant using soft nebulization promotes rapid spreading, similar to non‐nebulized surfactant, and remains robust under periodic compression–expansion cycles of the interface. The in vitro studies present a promising nebulization strategy for preserving both the surface activity and lamellar vesicle structures of surfactant‐based drugs, which could be key to enhancing their therapeutic effectiveness in aerosol drug delivery.