Surfactant-Stabilized Microbubbles as Ultrasound Contrast Agents: Stability Study of Span 60 and Tween 80 Mixtures Using a Langmuir Trough

Abstract

The sonication of mixtures of two nonionic surfactants, Span 60 and Tween 80, produces stable microbubbles which are being investigated as contrast agents for use in diagnostic ultrasound. The results of a previous unpublished study showed that stabilization of microbubbles does not occur when only one type of surfactant is used. The work presented here involves a study of the molecular associations of the surfactants around the microbubble “skin” that lead to stability. The resemblance of this system to a surfactant monolayer at an air/buffer interface suggested the use of a Langmuir trough to provide insight into the molecular parameters that promote stability. Similarity between the P-A curve for the microbubbles and curves obtained for solutions of surfactants at a molar ratio of 0.63 indicates there are 1.7 molecules of Span 60 to each Tween 80 molecule. This is further supported by the values obtained for the collapse pressure and area per molecule of microbubbles (40 mN/m and 32 Å2/ molecule) compared with the mixture at a 0.63 M ratio (50 mN/m and 31 Å2/molecule). In addition the same molar ratio was found to produce the highest yield of microbubbles during fabrication. The hypothesis of opposing forces was used to explain these interactions. The numbers suggest that incorporation of the correct proportion of Span molecules between the Tween molecules results in decreased head group repulsion, which lends stability to the microbubble. A molecular arrangement of these surfactant molecules around a microbubble is proposed. © 1993, American Chemical Society. All rights reserved.