Spectral imaging for microbubble characterisation
Spectral imaging for microbubble characterisation
Microbubbles stabilized by an outer lipid shell have been studied extensively for both diagnostic and therapeutic applications. The shell composition can significantly influence microbubble behavior, but performing quantitative measurements of shell properties is challenging. The aim of this study is to investigate the use of spectral imaging to characterize the surface properties of a range of microbubble formulations representing both commercial and research agents. A lipophilic dye, C-laurdan, whose fluorescence emission varies according to the properties of the local environment, was used to compare the degree and uniformity of the lipid order in the microbubble shell, and these measurements were compared with the acoustic response and stability of the different formulations. Spectral imaging was found to be suitable for performing rapid and hence relatively high throughput measurements of microbubble surface properties. Interestingly, despite significant differences in lipid molecule size and charge, all of the different formulations exhibited highly ordered lipid shells. Measurements of liposomes with the same composition and the debris generated by destroying lipid microbubbles with ultrasound (US) showed that these exhibited a lower and more varied lipid order than intact microbubbles. This suggests that the high lipid order of microbubbles is due primarily to compression of the shell as a result of surface tension and is only minimally affected by composition. This also explains the similarity in acoustic response observed between the formulations, because microbubble dynamics are determined by the diameter and shell viscoelastic properties that are themselves a function of the lipid order. Within each population, there was considerable variability in the lipid order and response between individual microbubbles, suggesting the need for improved manufacturing techniques. In addition, the difference in the lipid order between the shell and lipid debris may be important for therapeutic applications in which shedding of the shell material is exploited, for example, drug delivery.
609-617
Browning, Richard J.
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Aron, Miles
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Booth, Anna
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Rademeyer, Paul
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Wing, Sarah
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Brans, Veerle
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Shrivastava, Shamit
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Carugo, Dario
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Stride, Eleanor
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21 January 2020
Browning, Richard J.
32d183de-738d-49d7-8e74-af7b0a18e73f
Aron, Miles
4d9c7843-bbe5-4a5d-975f-ea58a09fc621
Booth, Anna
b1afd226-30b6-4ca6-9095-dcd54542c902
Rademeyer, Paul
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Wing, Sarah
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Brans, Veerle
ec8baff7-ffe7-4ba6-9beb-b1fc1fadf7cf
Shrivastava, Shamit
5207d595-1293-4d32-b9fd-7e4addfadaea
Carugo, Dario
0a4be6cd-e309-4ed8-a620-20256ce01179
Stride, Eleanor
c0143e95-81fa-47c8-b9bc-5b4fc319bba6
Browning, Richard J., Aron, Miles, Booth, Anna, Rademeyer, Paul, Wing, Sarah, Brans, Veerle, Shrivastava, Shamit, Carugo, Dario and Stride, Eleanor
(2020)
Spectral imaging for microbubble characterisation.
Langmuir, 36 (2), .
(doi:10.1021/acs.langmuir.9b03828).
Abstract
Microbubbles stabilized by an outer lipid shell have been studied extensively for both diagnostic and therapeutic applications. The shell composition can significantly influence microbubble behavior, but performing quantitative measurements of shell properties is challenging. The aim of this study is to investigate the use of spectral imaging to characterize the surface properties of a range of microbubble formulations representing both commercial and research agents. A lipophilic dye, C-laurdan, whose fluorescence emission varies according to the properties of the local environment, was used to compare the degree and uniformity of the lipid order in the microbubble shell, and these measurements were compared with the acoustic response and stability of the different formulations. Spectral imaging was found to be suitable for performing rapid and hence relatively high throughput measurements of microbubble surface properties. Interestingly, despite significant differences in lipid molecule size and charge, all of the different formulations exhibited highly ordered lipid shells. Measurements of liposomes with the same composition and the debris generated by destroying lipid microbubbles with ultrasound (US) showed that these exhibited a lower and more varied lipid order than intact microbubbles. This suggests that the high lipid order of microbubbles is due primarily to compression of the shell as a result of surface tension and is only minimally affected by composition. This also explains the similarity in acoustic response observed between the formulations, because microbubble dynamics are determined by the diameter and shell viscoelastic properties that are themselves a function of the lipid order. Within each population, there was considerable variability in the lipid order and response between individual microbubbles, suggesting the need for improved manufacturing techniques. In addition, the difference in the lipid order between the shell and lipid debris may be important for therapeutic applications in which shedding of the shell material is exploited, for example, drug delivery.
Text
Lipid formulation revised clean
- Accepted Manuscript
Text
Lipid formulation Supporting information
- Accepted Manuscript
More information
Accepted/In Press date: 19 December 2019
e-pub ahead of print date: 19 December 2019
Published date: 21 January 2020
Additional Information:
Funding Information:
The authors would like to acknowledge James Fisk and David Salisbury for their contribution to the design and construction of the experimental apparatus used in this work. Funding for the work was provided by the Engineering and Physical Sciences Research Council (EP/I021795/1 and EP/L024012/1) and the Institute of Engineering and Technology (AF Harvey Prize).
Publisher Copyright:
© 2019 American Chemical Society.
Identifiers
Local EPrints ID: 436853
URI: http://eprints.soton.ac.uk/id/eprint/436853
ISSN: 0743-7463
PURE UUID: f98960c3-cd0d-4074-b4ed-762c8f6669fe
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Date deposited: 13 Jan 2020 17:30
Last modified: 06 Jun 2024 04:22
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Contributors
Author:
Richard J. Browning
Author:
Miles Aron
Author:
Anna Booth
Author:
Paul Rademeyer
Author:
Sarah Wing
Author:
Veerle Brans
Author:
Shamit Shrivastava
Author:
Eleanor Stride
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