Concentration-Dependent Viscoelasticity of Poloxamer-Shelled Microbubbles.

The oscillation of shelled microbubbles during exposure to ultrasound is influenced by the mechanical properties of the shell components. The oscillation behavior of bubbles coated with various phospholipids and other amphiphiles has been studied. However, there have been few investigations of how the adsorption conditions of the shell molecules relate to the viscoelastic properties of the shell and influence the oscillation behavior of the bubbles. In the present study, we investigated the oscillation characteristics of microbubbles coated with a poloxamer surfactant, that is, Pluronic F-68, at several concentrations after the adsorption kinetics of the surfactant at the gas-water interface had reached equilibrium. The dilatational viscoelasticity of the shell during exposure to ultrasound was analyzed in the frequency domain from the attenuation characteristics of the acoustic pulses propagated in the bubble suspension. At Pluronic F-68 concentrations lower than 2.0 × 10-2 mol L-1, the attenuation characteristics typically exhibited a sharp peak. At concentrations higher than 2.0 × 10-2 mol L-1, the peak flattened. The dilatational elasticity and viscosity of the shell were estimated by fitting the theoretical model to the experimental values, which revealed that both the elasticity and viscosity increased markedly at approximately 2.0 × 10-2 mol L-1. This suggests that the adsorption properties of Pluronic F-68 strongly affect the oscillation characteristics of microbubbles of a size suitable for medical ultrasound diagnostics.

Vibration Characteristics and Persistence of Poloxamer- or Phospholipid-Coated Single Microbubbles under Ultrasound Irradiation.

Microbubbles shelled with soft materials are expected to find applications as ultrasound-sensitive drug delivery systems, including through sonoporation. Microbubbles with specific vibrational characteristics and long intravascular persistence are required for clinical uses. To achieve this aim, the kinetics of the microbubble shell components at the gas/liquid interface while being subjected to ultrasound need to be better understood. This paper investigates the vibration characteristics and lifetime of single microbubbles coated with a poloxamer surfactant, Pluronic F-68, and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) under ultrasound irradiation. Air- and perfluorohexane (PFH)-filled microbubbles coated with Pluronic F-68 and DMPC at several concentrations (0 to 10-2 mol L-1) were produced. An optical measurement system using a laser Doppler vibrometer and microscope was used to observe the radial vibration mode of single microbubbles. The vibrational displacement amplitude and resonance radius of Pluronic- or DMPC-coated microbubbles were found to depend very little on the concentrations. The resonance radius was around 65 µm at 38.8 kHz under all the experimental conditions investigated. The lifetime of the microbubbles was investigated simultaneously by measuring their temporal change in volume, and it was increased with Pluronic concentration. Remarkably, the oscillation amplitude of the bubble has an effect on the bubble lifetime. In other words, larger oscillation under the resonance condition accelerates the diffusion of the inner gas.

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

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.