Lung surfactant microbubbles

Abstract

The observation of stable microbubbles was instrumental to the discovery of lung surfactant and has been turned into a clinical tool for the prediction of neonatal respiratory distress syndrome. However, the colloidal properties of lung surfactant microbubbles have not been well characterized prior to this study. We show here that a common exogenous lung surfactant, Survanta, is capable of routinely stabilizing approximately a billion microbubbles per mL, most of which are less than 10 µm diameter, when perfluorobutane was used as the filling gas. The formulation therefore has remarkably rapid adsorption kinetics and surface tension lowering ability. The addition of an emulsifier did not significantly enhance microbubble production. Fluorescence microscopy showed prominent collapse structures on these microbubbles, and freeze-fracture electron microscopy showed undulation patterns of the monolayer surface. Zeta potential analysis indicated that Survanta microbubbles were highly negatively charged. Quantitative measurements of microbubble production allowed an analysis of competitive adsorption. Bovine serum albumin inhibited Survanta adsorption in a dose-response manner. Microbubble production was not reactivated by the addition of the nonionic polymer, poly(ethylene glycol). Lung surfactant microbubbles can serve as a tool to evaluate surfactant function and, potentially, as a theranostic agent for ultrasound.