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Establishment of a synthetic in vitro lung surfactant model for particle interaction studies on a Langmuir film balance.

With an intention to provide a robust and economical model that can be used for predicting particle interactions with the pulmonary surfactant, the aim of this study was to find an artificial surfactant model which perfectly mimics the properties of natural pulmonary surfactant. A surfactant model should be reproducible, robust and predict interactions between pulmonary surfactant and exogenous influences from the air and the aqueous site. We compared three synthetic models with the natural bovine surfactant Alveofact®. The lung conditions were simulated by spreading the surfactants at the air/aqueous interface on a Langmuir trough with movable barriers. All three artificial surfactant models showed properties very similar to those of Alveofact®. The visualization of the monolayers by AFM revealed very similar structures with domain formation. The Tanaka lipid mixture has already shown good results in-vitro and in-vivo in previous studies. The DPPC-DOPC model has large conformations in the surface pressure isotherms and showed a biomimetic exclusion plateau indicative of an effective lung surfactant formulation. Also the equilibrium spreading pressure was similar. DPPC-POPG had the greatest similarities with Alveofact® in the hysteresis areas. The kinetic constants of the relaxation experiments during desorption showed that the PCPG model (at 30 mN/m) had almost identical diffusion and dissolution values as Alveofact®. As proof of concept, the interaction of the models with PLGA nanoparticles, showed promising results in all experiments for all three surfactant models. The results show that the choice of components in a model play a crucial role for reproducible results. The selected models can be used for further studies as synthetic in-vitro lung models.