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

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.

KEYWORDS:

• Corticosteroids
• cortisone
• lung surfactant monolayer
• molecular dynamics simulation
• drug-lipid interactions

Acknowledgement

This work was conducted with the support of University of Technology Sydney (UTS) FEIT Research Scholarship and UTS International Research Scholarship (Mohammad Zohurul Islam). The computational facilities were provided by the UTS eResearch High-Performance Computer Cluster and NCI Australia.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data accessibility

All data are presented in the paper in either figure or tabular form. The data are also provided in the electronic supplementary material.

Authors’ contributions

M.Z.I. performed the simulations, data analysis, participated in the design of the study and drafted the original manuscript. S.I.H. edited the manuscript. E.D. supervised M.Z.I. and critically revised the manuscript, and S.C.S. developed the concept, supervised M.Z.I. and edited the manuscript. All authors gave final approval for publication and agreed to be held accountable for the work performed therein.

Additional information

Funding

E.D. was funded by the UTS Chancellor’s Postdoctoral Research Fellowship scheme.