Behavior of Microbubbles on Air–Aqueous Interfaces

Animal-derived lung surfactants have saved millions of lives of preterm neonates with neonatal Respiratory Distress Syndrome (nRDS). However, a replacement for animal-derived lung surfactants has been sought for decades due to its high manufacturing cost, inaccessibility in low-income countries, and failure to show efficacy when nebulized. This study investigated the use of lipid-coated microbubbles as potential replacements for exogenous lung surfactants. Three different formulations of microbubbles (DPPC with/out PEG40-stearate and poractant alfa) were prepared, and their equilibrium and dynamic surface tensions were tested on a clean air-saline interface or a simulated air-lung fluid interface using a Langmuir-Blodgett trough. In dynamic surface measurements, microbubbles reduced the minimum surface tension compared with the equivalent composition lipid suspension: e.g., PEG-free microbubbles had a minimum surface tension of 4.3 mN/m while the corresponding lipid suspension and poractant alfa had 20.4 (<i>p</i> ≤ 0.0001) and 21.8 mN/m (<i>p</i> ≤ 0.0001), respectively. Two potential mechanisms for the reduction of surface tension were found: Fragmentation of the foams created by microbubble coalescence; and clustering of microbubbles in the aqueous subphase disrupting the interfacial phospholipid monolayer. The predominant mechanism appears to depend on the formulation and/or the environment. The use of microbubbles as a replacement for exogenous lung surfactant products thus shows promise and further work is needed to evaluate efficacy in vivo.