Glucocorticoids are widely employed in various lung diseases including asthma, chronic obstructive pulmonary disease, bronchitis, emphysema, and respiratory allergies. When the glucocorticoid is administrated orally, intravenously, or topically, then they might cause a lot of side effects by systemic pathway, i.e. the drug enters the bloodstream. Therefore, for the treatment of lung disease, the preferred route is by inhalation, which is capable of avoiding such systemic side effects. Clinical trials are being conducted to test new delivery routes such as aerosol inhalation. Corticosteroids can reduce airways’ inflammation in the conducting zone of the lower airways and at the microphagic zone in the deeper lung airways at alveoli. The drugs reduce inflammation by several mechanisms; one includes the binding of the drug to corticosteroid receptors, which then causes cell internal effects, and the other is interaction with the lung surfactants that line at air-water interface in alveoli. Therefore, it is essential to understand the interaction, deposition, and spreading mechanism of corticosteroid in lung surfactants.

This study focuses on the interaction of glucocorticoid drug (especially mometasone furoate) with the lung surfactants at alveoli in the peripheral lung. Specifically, this investigation is aimed to understand the concentration-dependent effect of glucocorticoid drug mometasone furoate on the lung surfactant monolayer that forms the main air-water interface in the alveoli.

Another reason for studying the mometasone furoate interaction with the lung surfactant monolayer (LSM) is because it can be delivered to alveoli with the mixture of exogenous lung surfactants (Bovine lipid extract surfactant, Survantan, Curosurf, Infasurf and Exosurf). Glucocorticoid with exogenous lung surfactant might help the respiratory process of preterm infants with underdeveloped lungs and deficiency in surfactant formation of the patients suffering from respiratory distress syndrome. Using exogenous animal sources of lung surfactant is now a well-established therapy in clinical procedures, resulting in a significant reduction in preterm baby mortality. Pulmonary surfactant was replaced in babies with meconium aspiration syndrome and adults with chronic respiratory disorders. The outcomes, however, were not equally effective in treating people with such medical issues. As a result, the therapeutic application of a combination of pulmonary surfactant and glucocorticoids to treat lung diseases would be a significant step forward in healthcare. The adverse side effects of glucocorticoids can significantly be minimised by the inhalation drug administration technique. However, molecular interactions from experiments with glucocorticoids are unclear, and further research into the lung surfactant stability and mechanical properties is required to understand how to deliver glucocorticoid drugs into the targeted region of the alveoli by avoiding lung surfactant damage. At this time, drug interaction with lung surfactant has enabled the development of more effective and less intrusive methods for effective dosage, controlled corticosteroid release, and off-targeting drug deposition on LSM. To overcome physicochemical and biological constraints, smart delivery systems require a thorough understanding of molecular interactions as well as biophysical features at the molecular scale.

To understand glucocorticoid interaction with LSM at the molecular level, the combination of Langmuir monolayer and classical molecular dynamics (MD) study have been proven to be an effective technique for understanding the interactions of complicated biological systems. Coarse grained MD simulations have been particularly useful to study complex biological models involving lipids and proteins in cell membranes, lipid vesicle, lipid monolayer, lipid bilayer, and the interaction of such lipid systems with proteins or drug-like small molecules. Because these phenomena occur over a longer time and larger length scales, CG MD study can be capable of reducing computational time significantly with a reliable level of accuracy. In the context of lung surfactants, CG MD simulations have been extensively used to investigate pulmonary surfactant biophysical processes such as monolayer collapsing mechanism, monolayer stability, phase coexistence, monolayer compressibility, and monolayer dynamical characteristics.