Biophisical Evaluation of Drug Impact on Pulmonary Surfactant Performance

Abstract

The respiratory surface of the mammalian's lung is covered by a thin aqueous layer, and on top of it, by a lipid-protein surface active material, the pulmonary surfactant (PS). It is synthesised by type II pneumocytes and secreted in the form of multilamellar structures. Its main function is to form a film to reduce the surface tension at the air-liquid interface to values below 2mN/m, to prevent pulmonary collapse during expiration and to minimize the work during inspiration. PS has unique biophysical properties to adsorb very rapidly (in few seconds) into the air-liquid interface and, once there, to spread efficiently along it. The pulmonary surfactant system, historically considered as a barrier to drug delivery, could therefore offer novel opportunities to vehiculize different drugs efficiently, while hiding and protecting them from clearence in the lung. Nevertheless, drug impact on pulmonary surfactant performance needs to be considered in a case by case basis when different molecular entities are combined with PS.In the present work we have investigated the effect of the interaction of an anti-inflammatory steroid and an anti-tuberculosis drug with different pulmonary surfactant preparations, and how drug effects depend on PS composition. After combining properly different surfactant systems with each drug at different drug/lipid ratios, we have evaluated their impact on surfactant function and mechanical properties of surfactant layers, as assessed in a captive bubble surfactometer. Furthermore, we have used the Langmuir-Blodgett technique to prepare supported films and analyse the structure of different drug-loaded surfactant layers in order to detect structural changes associated with the impact of drugs on surfactant activity.