The interface between alveoli and air in our lungs is lined with lung surfactant, a mixture of lipids and proteins that facilitates breathing by reducing the air/water interfacial tension. Infants born prematurely before their thirty-second gestation week often develop neonatal respiratory distress syndrome (NRDS) due to a lack of functional surfactant. In adults and children, lung injury or disease (including Covid-19 infection) can lead to lung surfactant inactivation resulting in acute respiratory distress syndrome (ARDS). ARDS manifest similar symptoms, but has mortality rates of 40%. Current NRDS treatment is intratracheal delivery of replacement lung surfactants derived from animal sources. There is no viable ARDS treatment. It is hypothesized that surfactant inactivation in ARDS is caused by the co-adsorption of serum proteins or inflammation products such as lysolipids to the alveolar air-water interface which prevent the adsorption and/or function of normally sufficient amounts of lung surfactant. We and others have found that adding low molecular weight hydrophilic polymers such as polyethylene glycol or dextran can promote the adsorption of lung surfactant due to depletion attraction. However, adding polymers to the suspensions likely alters the rheological properties of the lung surfactant suspensions which may cause difficulty in delivery or subsequent surfactant spreading in the lung. This work investigates the bulk rheology of three clinical lung surfactant suspensions commonly used in the USA: Survanta (bovine lung surfactant extract), Curosurf (porcine lung surfactant extract), and Infasurf (calf lung surfactant extract), to understand factors affecting the efficiency of surfactant intratracheal delivery. These suspensions are prepared from solvent extracted bovine or porcine lung surfactant that is resuspended in saline at various concentrations. The effects of polyethylene glycol (PEG, known to reverse surfactant inactivation in ARDS) on the flow properties of the surfactants are also investigated.
The three surfactant suspensions exhibit dramatic, orders of magnitude shear-thinning (reduced viscosity with increased rate of shear) behavior over the shear range expected during delivery and spreading in the lung. Surprisingly, the viscosity is not simply related to the lipid mass fraction in the suspension as is typical for a hard-sphere colloidal system. Optical and electron microscopy and small-angle X-ray scattering show that the viscosity variation is due to the temperature and composition-dependent structure of the surfactant aggregates. Survanta forms crystalline, asymmetric particles with large aspect ratios. Infasurf organizes into aggregates of unilamellar vesicles containing water pockets. Curosurf forms onion-like multi-layered liposomes. The difference in structure is dictated by each surfactantâs unique composition and the different structures lead to different effective volume fractions which are responsible for the difference in their measured viscosities. Adding PEG dehydrates the surfactant aggregates, thereby decreasing the suspension volume fraction, which lowers the suspension viscosity, even though the PEG increases the continuous fluid viscosity. The data helps explain clinical differences in breathing restoration time following intratracheal surfactant delivery in babies among the three surfactants. These studies are crucial in formulating synthetic lung surfactant replacement that can both treat the RDSs effectively and reach the lung periphery rapidly.
