Concentration-dependent cortisone adsorption and interaction with model lung surfactant monolayer

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Abstract
Corticosteroids are drugs used to treat inflammatory conditions. In the case of lung diseases, corticosteroids can be administered by inhalation. The main barrier for inhaled particles is the lung surfactant monolayer (LSM) that lines the alveolar air–water interface and reduces surface tension during breathing. In this study, we use coarse-grained molecular dynamics simulations to study the concentration-dependent interaction of cortisone with an LSM composed of neutral and negatively charged phospholipids, cholesterol, and surfactant proteins. Simulations were carried out at surface tensions mimicking inhalation and exhalation conditions and different compressibilities. In-depth analysis shows that cortisone causes a concentration-dependent expansion of the monolayer that at high surface tension and high drug concentrations results in the monolayer collapsing. This instability is associated with the accumulation of drugs and surfactant proteins that prevent adsorption into the monolayer. Our findings help to improve the understanding of how corticosteroids alter lung surfactants structure and assist efforts to improve drug adsorption.

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