Microbubbles with a Self-Assembled Poloxamer Shell and a Fluorocarbon Inner Gas.

Abstract

The numerous applications of microbubbles in food science and medicine call for a better understanding and control of the effects of the properties of their shells on their stability and ability to resonate at chosen frequencies when submitted to an ultrasound field. We have investigated both millimetric and micrometric bubbles stabilized by an amphiphilic block copolymer, Poloxamer 188 (e.g., Pluronic F-68). Although Pluronic F-68 is routinely being used as a dispersing and foaming agent to facilitate phospholipid-based microbubble preparation, it has never been studied as a shell component per se. First, we investigated the adsorption kinetics of Pluronic F-68 at the interface between water and air, or air saturated with vapors of perfluorohexane (F-hexane), using bubble profile tensiometry analysis. F-Hexane was found to strongly accelerate the adsorption of Pluronic F-68 (at low concentrations) and decrease the interfacial tension values at equilibrium (at all concentrations). We also found that relatively stable microbubbles could unexpectedly be prepared from Pluronic F-68 in the absence of any other surfactant, but only when F-hexane was present. These bubbles showed an only limited volume increase over ∼3 h, while a 10-fold increase in size occurred within 200 s in the absence of a fluorocarbon. Remarkably, their deflation rate decreased when the Pluronic F-68 concentration decreased, suggesting that bubbles with semidilute copolymer coverage are more stable than those more densely covered by copolymer brushes. Single-bubble experiments using laser Doppler vibratometry showed that, by contrast with other surfactant-coated microbubbles, the resonance radius of the Pluronic F-68-coated microbubbles was lower than that of naked microbubbles, meaning that they are less elastic. It was also found that the bubble's vibrational displacement amplitude decreased substantially when the microbubbles were covered with Pluronic F-68, an effect that was further amplified by F-hexane.