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    Concentration-Dependent Effect of the Steroid Drug Prednisolone on a Lung Surfactant Monolayer

    Year: 2022

    Journal: Langmuir, Volume 38, APR 12, page 4188–4199

    Authors: Islam, Mohammad Zohurul; Krajewska, Martyna; Hossain, Sheikh, I; Prochaska, Krystyna; Anwar, Azraf; Deplazes, Evelyne; Saha, Suvash C.

    Organizations: University of Technology Sydney (UTS) FEIT Research Scholarship, UTS International Research Scholarship; UTS Chancellor's Postdoctoral Fellowship scheme

    The lung surfactant monolayer (LSM) is the main barrier for particles entering the lung, including steroid drugs used to treat lung diseases. The present study combines Langmuir experiments and coarse-grained (CG) molecular dynamics simulations to investigate the concentration-dependent effect of steroid drug prednisolone on the structure and morphology of a model LSM. The surface pressure-area isotherms for the Langmuir monolayers reveal a concentration-dependent decrease in area per lipid (APL). Results from simulations at a fixed surface tension, representing inhalation and exhalation conditions, suggest that at high drug concentrations, prednisolone induces a collapse of the LSM, which is likely caused by the inability of the drug to diffuse into the bilayer. Overall, the monolayer is most susceptible to drug-induced collapse at surface tensions representing exhalation conditions. The presence of cholesterol also exacerbates the instability. The findings of this investigation might be helpful for better understanding the interaction between steroid drug prednisolone and lung surfactants in relation to off-target effects.
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