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

The role of PEG-40-stearate in the production, morphology and stability of microbubbles
The role of PEG-40-stearate in the production, morphology and stability of microbubbles
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 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.
0743-7463
Owen, Joshua
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Kamila, Sukanta
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Shrivastava, Shamit
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Carugo, Dario
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Bernardino de la Serna, Jorge
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Mannaris, Christophoros
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Pereno, Valerio
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Browning, Richard J.
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Beguin, Estelle
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McHale, Anthony Patrick
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Callan, John F.
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Stride, Eleanor
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Owen, Joshua
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Kamila, Sukanta
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Shrivastava, Shamit
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Carugo, Dario
0a4be6cd-e309-4ed8-a620-20256ce01179
Bernardino de la Serna, Jorge
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Mannaris, Christophoros
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Pereno, Valerio
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Browning, Richard J.
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Beguin, Estelle
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McHale, Anthony Patrick
b70f9570-4254-451d-9723-b9d98e7c048c
Callan, John F.
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Stride, Eleanor
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Owen, Joshua, Kamila, Sukanta, Shrivastava, Shamit, Carugo, Dario, Bernardino de la Serna, Jorge, Mannaris, Christophoros, Pereno, Valerio, Browning, Richard J., Beguin, Estelle, McHale, Anthony Patrick, Callan, John F. and Stride, Eleanor (2018) The role of PEG-40-stearate in the production, morphology and stability of microbubbles. Langmuir. (doi:10.1021/acs.langmuir.8b02516).

Record type: Article

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 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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Accepted/In Press date: 28 November 2018
e-pub ahead of print date: 28 November 2018

Identifiers

Local EPrints ID: 426706
URI: http://eprints.soton.ac.uk/id/eprint/426706
ISSN: 0743-7463
PURE UUID: adb28c1c-1d7b-4ec8-8e9a-740425a31eec

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Date deposited: 10 Dec 2018 17:31
Last modified: 30 Jan 2020 05:07

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Contributors

Author: Joshua Owen
Author: Sukanta Kamila
Author: Shamit Shrivastava
Author: Dario Carugo
Author: Jorge Bernardino de la Serna
Author: Christophoros Mannaris
Author: Valerio Pereno
Author: Richard J. Browning
Author: Estelle Beguin
Author: Anthony Patrick McHale
Author: John F. Callan
Author: Eleanor Stride

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