Effect of Temperature on Stability of Lipid Microbubbles

Abstract

The effect of temperature on stability of lipid microbubble shell containing polyethyleneoxide-40-stearate (PEG₄₀St) as emulsifier was investigated. Microbubbles at 4 °C were subjected to different temperatures up to 48 ºC (down-to-up) and it was found that both the number and the size of microbubbles remained unchanged in the population up to a certain time, so called “onset time”. The onset time was about 6 hrs at 10 °C, 2 hrs at 20 °C and shorter at elevated temperatures, exhibiting an exponential decrease with increasing temperature. Once the onset time was reached, the number of microbubbles started to decrease and the average size of the population started to increase. Observation of single microbubbles on a constant temperature heating stage exhibited that each microbubble had its own onset time, with the smaller microbubbles vanishing earlier than the larger ones. The Langmuir monolayer studies showed that hydration degree of the emulsifier PEG chains decreased with temperature, causing them go through conformational changes and subsequently destabilization of the shell. By subjecting the freshly produced microbubbles directly to the desired temperatures in up-to-down fashion, more stable microbubbles were able to be produced, with their onset time increased 40% at 10 °C to 500% at 38 °C. Overall, the results suggest that the new strategies need to be developed to control the collapse process in the microbubble shell resulting from the conformational changes in the PEG chains of the emulsifier for the design of more stable microbubbles.

Keywords

• Langmuir monolayers,phosholipids,PEG conformations,emulsifier,Microbubble,ultrasound contrast agent

Supporting Institution

Tubitak

Project Number

109M494

Thanks

The author would like to thank The Scientific and Technological Research Council of Turkey (TUBITAK) for the financial support through the project number of 109M494.

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