The steroid mometasone alters protein containing lung surfactant monolayers in a concentration-dependent manner

Mometasone is an investigational anti-inflammatory steroidal drug to treat inflammation via pulmonary administration. For steroid drugs to be effective they need to be adsorbed by lung surfactants, a thin monolayer at the air-water interface in alveoli that reduces surface tension. Information on the molecular-level interactions of the drug with lung surfactants is useful to understand the mechanism of adsorption. In this study, we use coarse-grained molecular dynamics simulation to understand the concentration-dependent effect of mometasone on a lung surfactant monolayer (LSM) composed of lipids and surfactant proteins, under two different breathing conditions (exhalation, at surface tension 0 mNm^-1 and inhalation, surface tension 20-25 mNm^-1). A series of fixed-APL and fixed-surface tension simulations were used to demonstrate that in the absence of drugs, the model LSM reproduces the surface tensions for the compressed and expanded states, as well as compressibility at different surface tensions. In-depth analysis of simulations of a LSM in the presence of five different drug concentrations shows that mometasone alters the structure and dynamics of the LSM in a concentration-dependent manner. Mometasone induces a collapse in the monolayer that is affected by the surfactant protein and surface tension. Overall, these findings suggest that the surfactant proteins, surface tension and drug concentration are all critical components affecting monolayer stability and drug adsorption. The outcomes of this study may be beneficial for a more in-depth understanding of how mometasone is adsorbed by lung surfactants.