The concentration-dependent effect of hydrocortisone on the structure of model lung surfactant monolayer by using an in silico approach

Understanding the adsorption mechanism of corticosteroids in the lung surfactant requires the knowledge of corticosteroid molecular interactions with lung surfactant monolayer (LSM). We employed coarse-grained molecular dynamics simulation to explore the action of hydrocortisone on an LSM comprised of a phospholipid, cholesterol and surfactant protein. The structural and dynamical morphology of the lung surfactant monolayer at different surface tensions were investigated to assess the monolayer compressibility. The simulations were also conducted at the two extreme ends of breathing cycles: exhalation (0 mN m(−1) surface tension) and inhalation (20 mN m(−1) surface tension). The impact of surface tension and hydrocortisone concentration on the monolayer compressibility and stability are significant, resulting the monolayer expansion at higher surface tension. However, at low surface tension, the highly compressed monolayer induces monolayer instability in the presence of the drug due to the accumulation of surfactant protein and drug. The constant area per lipid simulation results demonstrate that the surface pressure-area isotherms show a decrease in area-per-lipid with increased drug concentration. The drug-induced expansion causes considerable instability in the monolayer after a specific drug concentration is attained at inhalation breathing condition, whereas, for exhalation breathing, the monolayer gets more compressed, causing the LSM to collapse. The monolayer collapse occurs for inhalation due to the higher drug concentration, whereas for exhalation due to the accumulation of surfactant proteins and drugs. The findings from this study will aid in enhancing the knowledge of molecular interactions of corticosteroid drugs with lung surfactants to treat respiratory diseases.