Influence of selected inhalation drugs on dynamic physicochemical properties of a pulmonary surfactant model

Authors:

• Justyna Szczepańska,
• Katarzyna Ewa Dobrowolska,
• Tomasz Robert Sosnowski

Abstract

Pulmonary surfactant (PS) is a thin lipoprotein complex covering the whole alveolar surface. One of its main features is the ability to reduce surface tension at the air-liquid interface during the breathing cycle. Pulmonary surfactant works as a natural barrier impeding the particle penetration deeper into the human body, what is crucial in the terms of different kinds of molecules deposition in the lower respiratory tract. Physicochemical properties of the pulmonary surfactant are involved in the elimination of deposited particles (e.g. dust particles, but also inhaled therapeutic aerosols). Thus, it is necessary to investigate whether inhaled aerosols, including drugs, have any negative impact on both structure and physicochemical properties of PS, including its ability to adsorb at the air-liquid interface inside the alveoli. The aim of this work was to investigate the impact of three different inhalation anti-asthmatic drugs at various concentrations on the pulmonary surfactant model under dynamic conditions simulating the breathing cycle, and then to analyze these results in terms of surfactant physiology. The measurements were conducted with a pendant drop technique using a profile analysis tensiometer PAT-1M. This method enabled studying the surface tension both at constant interfacial area and also during breathing-like surface oscillations for tracking the changes in the surface rheological properties. Additionally, surface tension hysteresis for all the samples was determined. Comparison of this hysteresis allowed to detect disturbances in the interfacial dynamics, which might help to identify abnormalities in the functioning of PS. The changes of the interfacial properties such as the surface tension and the dilatational rheological parameters of the gas-liquid interface (dilatational elasticity and viscosity) were detected and this enabled drawing certain conclusions regarding the influence of different inhaled therapeutics on the dynamic surface properties of the PS. These interactions largely depend on the type of drug, the inhaled dose (i.e. final concentration in the system), as well as on the whole composition of the inhaled therapeutic formulation that may contain additional surfactants.