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

Abstract

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.

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

“…The interactions of corticosteroid drug hydrocortisone with LSM model appear to be very comparable to other corticosteroid drugs prednisone, 28,50,81 cortisone 82 or mometasone. 45 As a result of the structural similarities in corticosteroid drugs, it may be possible to generalise the fates of corticosteroids in lung surfactants.…”

“…The phase behaviour of the monolayer can be expressed in a function of the surface pressure and surface tension according to the equation p = g a-w − g eq , where, p is the pressure, g a-w (∼72 mN m −1 at 310 K) is the surface tension of the pure water at the air-water interface, and g eq is the surface tension of the monolayer. [27][28][29] Monolayer phase transition from LC phase to LE phase induced from the high surface pressure to low surface pressure, respectively. Due to the complexity of the LSM and changing the structure of LSM during breathing cycles, understanding the interaction of inhaled drug such as corticosteroid drugs is not trivial.…”

Effect of Silica Microparticles on Interactions in Mono- and Multicomponent Membranes

“…One of the biomimetic membrane systems used are lipid monolayers, which are often composed of DPPC, which is a component of the erythrocyte membrane or pulmonary surfactant. In addition, other lipids such as cholesterol (Chol) or proteins are also added to form multicomponent monolayers [ 13 , 14 , 15 ]. Monolayers are formed at the air–water interface, which allows for the acquisition of a lot of information about the interactions and the physicochemical properties of its components.…”