The role of PEG-40-stearate in the production, morphology and stability of microbubbles

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Abstract

Phospholipid coated microbubbles are currently in widespread clinical use as ultrasound contrast agents and under investigation for therapeutic applications. Previous studies have demonstrated the importance of the coating nanostructure in determining microbubble stability and its dependence upon both composition and processing method. Whilst the influence of different phospholipids has been widely investigated, the role of other constituents such as emulsifiers has received comparatively little attention. Herein, we present an examination of the impact of polyethylene glycol (PEG) derivatives upon microbubble structure and properties. We present data using both pegylated phospholipids and a fluorescent PEG-40-stearate analogue synthesised in house to directly observe its distribution in the microbubble coating. We examine microbubbles of clinically relevant sizes, investigating both their surface properties and population size distribution and stability. Domain formation was only observed on the surface of larger microbubbles, which were found to contain a higher concentration of PEG-40-stearate. Lipid analogue dyes were also found to influence domain formation compared with PEG-40-stearate alone. “Squeezing out” of PEG-40-stearate was not observed from any of the microbubble sizes investigated. At the ambient temperature, microbubbles formulated with DSPE-PEG(2000) were found to be more stable than those containing PEG-40-stearate. At 37 °C, however the stability in serum was found to be the same for both formulations and no difference in acoustic backscatter was detected. This could potentially reduce the cost of PEGylated microbubbles and facilitate simpler attachment of targeting or therapeutic species. However, whether PEG-40-stearate sufficiently shields microbubbles to inhibit physiological clearance mechanisms still requires investigation.
LanguageEnglish
JournalLangmuir
Early online date28 Nov 2018
DOIs
Publication statusE-pub ahead of print - 28 Nov 2018

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Stearates
stearates
Polyethylene glycols
glycols
polyethylenes
Phospholipids
Coatings
analogs
coatings
clearances
Contrast Media
Surface properties
compressing
Nanostructures
serums
surface properties
Lipids
Coloring Agents
ambient temperature
attachment

Keywords

  • Microbubbles

Cite this

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title = "The role of PEG-40-stearate in the production, morphology and stability of microbubbles",
abstract = "Phospholipid coated microbubbles are currently in widespread clinical use as ultrasound contrast agents and under investigation for therapeutic applications. Previous studies have demonstrated the importance of the coating nanostructure in determining microbubble stability and its dependence upon both composition and processing method. Whilst the influence of different phospholipids has been widely investigated, the role of other constituents such as emulsifiers has received comparatively little attention. Herein, we present an examination of the impact of polyethylene glycol (PEG) derivatives upon microbubble structure and properties. We present data using both pegylated phospholipids and a fluorescent PEG-40-stearate analogue synthesised in house to directly observe its distribution in the microbubble coating. We examine microbubbles of clinically relevant sizes, investigating both their surface properties and population size distribution and stability. Domain formation was only observed on the surface of larger microbubbles, which were found to contain a higher concentration of PEG-40-stearate. Lipid analogue dyes were also found to influence domain formation compared with PEG-40-stearate alone. “Squeezing out” of PEG-40-stearate was not observed from any of the microbubble sizes investigated. At the ambient temperature, microbubbles formulated with DSPE-PEG(2000) were found to be more stable than those containing PEG-40-stearate. At 37 °C, however the stability in serum was found to be the same for both formulations and no difference in acoustic backscatter was detected. This could potentially reduce the cost of PEGylated microbubbles and facilitate simpler attachment of targeting or therapeutic species. However, whether PEG-40-stearate sufficiently shields microbubbles to inhibit physiological clearance mechanisms still requires investigation.",
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author = "J Callan and Sukanta Kamila and McHale, {Anthony P.}",
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AU - Kamila, Sukanta

AU - McHale, Anthony P.

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N2 - Phospholipid coated microbubbles are currently in widespread clinical use as ultrasound contrast agents and under investigation for therapeutic applications. Previous studies have demonstrated the importance of the coating nanostructure in determining microbubble stability and its dependence upon both composition and processing method. Whilst the influence of different phospholipids has been widely investigated, the role of other constituents such as emulsifiers has received comparatively little attention. Herein, we present an examination of the impact of polyethylene glycol (PEG) derivatives upon microbubble structure and properties. We present data using both pegylated phospholipids and a fluorescent PEG-40-stearate analogue synthesised in house to directly observe its distribution in the microbubble coating. We examine microbubbles of clinically relevant sizes, investigating both their surface properties and population size distribution and stability. Domain formation was only observed on the surface of larger microbubbles, which were found to contain a higher concentration of PEG-40-stearate. Lipid analogue dyes were also found to influence domain formation compared with PEG-40-stearate alone. “Squeezing out” of PEG-40-stearate was not observed from any of the microbubble sizes investigated. At the ambient temperature, microbubbles formulated with DSPE-PEG(2000) were found to be more stable than those containing PEG-40-stearate. At 37 °C, however the stability in serum was found to be the same for both formulations and no difference in acoustic backscatter was detected. This could potentially reduce the cost of PEGylated microbubbles and facilitate simpler attachment of targeting or therapeutic species. However, whether PEG-40-stearate sufficiently shields microbubbles to inhibit physiological clearance mechanisms still requires investigation.

AB - Phospholipid coated microbubbles are currently in widespread clinical use as ultrasound contrast agents and under investigation for therapeutic applications. Previous studies have demonstrated the importance of the coating nanostructure in determining microbubble stability and its dependence upon both composition and processing method. Whilst the influence of different phospholipids has been widely investigated, the role of other constituents such as emulsifiers has received comparatively little attention. Herein, we present an examination of the impact of polyethylene glycol (PEG) derivatives upon microbubble structure and properties. We present data using both pegylated phospholipids and a fluorescent PEG-40-stearate analogue synthesised in house to directly observe its distribution in the microbubble coating. We examine microbubbles of clinically relevant sizes, investigating both their surface properties and population size distribution and stability. Domain formation was only observed on the surface of larger microbubbles, which were found to contain a higher concentration of PEG-40-stearate. Lipid analogue dyes were also found to influence domain formation compared with PEG-40-stearate alone. “Squeezing out” of PEG-40-stearate was not observed from any of the microbubble sizes investigated. At the ambient temperature, microbubbles formulated with DSPE-PEG(2000) were found to be more stable than those containing PEG-40-stearate. At 37 °C, however the stability in serum was found to be the same for both formulations and no difference in acoustic backscatter was detected. This could potentially reduce the cost of PEGylated microbubbles and facilitate simpler attachment of targeting or therapeutic species. However, whether PEG-40-stearate sufficiently shields microbubbles to inhibit physiological clearance mechanisms still requires investigation.

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