Novel ultrasound contrast agent based on microbubbles generated from surfactant mixtures of Span 60 and polyoxyethylene 40 stearate.
In this study, novel perfluorocarbon-filled microbubbles as ultrasound contrast agent were fabricated using ultrasonication of a surfactant mixture of sorbitan monostearate (Span 60) and polyoxyethylene 40 stearate (PEG40S) in aqueous media. The microbubbles generated from a 1:9 mixture of PEG40S/Span 60 exhibited an average diameter of 2.08+/-1.27 microm. More than 99% of the microbubbles had a mean particle diameter less than 8 microm, indicating that they were appropriately sized for intravenous administration as ultrasound contrast agent. The stabilization mechanism of the microbubbles was investigated by the Langmuir-Blodgett technique including the measurements of surface pressure-area (pi-A) isotherms and compression-decompression cycles with a two-dimensional monolayer of Span 60 and PEG40S. The dependence on molar fraction of PEG40S in pi-A isotherms of mixed monolayers provided a strong evidence of interactions between the two microbubble-forming materials. It is suggested that the monolayer shell imparts good stability to the microbubbles by three means: (1) a low surface tension monolayer hinders dissolution through the reduction of surface tension, which introduces a mechanical surface pressure that counters the Laplace pressure; (2) the presence of a monolayer shell imparts a significant barrier to gas escaping from the core into the aqueous medium; and (3) encapsulation elasticity stabilizes microbubbles against diffusion-driven dissolution and explains the long shelf-life of microbubble contrast agent. The preliminary in vivo ultrasound imaging study showed that such stabilized microbubbles demonstrated excellent enhancement under grey-scale pulse inversion harmonic imaging and power Doppler imaging.
Xing
Zhanwen
Z
Nanobiotechnology Division, Bio-X Center, State Key Laboratory of Urban Water Resources and Environment, School of Science Harbin Institute of Technology, Harbin 150080, China.
Ke
Hengte
H
Wang
Jinrui
J
Zhao
Bo
B
Yue
Xiuli
X
Dai
Zhifei
Z
Liu
Jibin
J
D000818:Animals; D003287:Contrast Media; D003952:Diagnostic Imaging / Q000379:methods*; D006601:Hexoses / Q000737:chemistry; D007668:Kidney / Q000000981:diagnostic imaging; D045423:Microbubbles; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011312:Pressure; D011817:Rabbits; D013501:Surface-Active Agents; D013696:Temperature; D014465:Ultrasonics; D014463:Ultrasonography
D003287:Contrast Media; D006601:Hexoses; D013501:Surface-Active Agents; C526284:polyoxyethylene 40 stearate; D011092:Polyethylene Glycols; C009298:sorbitan monostearate