A single short 'tone burst' results in optimal drug delivery to tumours using ultrasound-triggered therapeutic microbubbles

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Publication date
2022-03Author
Ingram, N.McVeigh, L.E.
Abou-Saleh, R.H.
Batchelor, D.V.B.
Loadman, Paul

McLaughlan, J.R.
Markham, A.F.
Evans, S.D.
Coletta, P.L.
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© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Peer-Reviewed
YesOpen Access status
openAccessAccepted for publication
2022-03-09
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Advanced drug delivery systems, such as ultrasound-mediated drug delivery, show great promise for increasing the therapeutic index. Improvements in delivery by altering the ultrasound parameters have been studied heavily in vitro but relatively little in vivo. Here, the same therapeutic microbubble and tumour type are used to determine whether altering ultrasound parameters can improve drug delivery. Liposomes were loaded with SN38 and attached via avidin: biotin linkages to microbubbles. The whole structure was targeted to the tumour vasculature by the addition of anti-vascular endothelial growth factor receptor 2 antibodies. Tumour drug delivery and metabolism were quantified in SW480 xenografts after application of an ultrasound trigger to the tumour region. Increasing the trigger duration from 5 s to 2 min or increasing the number of 5 s triggers did not improve drug delivery, nor did changing to a chirp trigger designed to stimulate a greater proportion of the microbubble population, although this did show that the short tone trigger resulted in greater release of free SN38. Examination of ultrasound triggers in vivo to improve drug delivery is justified as there are multiple mechanisms at play that may not allow direct translation from in vitro findings. In this setting, a short tone burst gives the best ultrasound parameters for tumoural drug delivery.Version
Published versionCitation
Ingram N, McVeigh LE, Abou-Saleh RH et al (2022) A single short 'tone burst' results in optimal drug delivery to tumours using ultrasound-triggered therapeutic microbubbles. Pharmaceutics. 14(3): 622.Link to Version of Record
https://doi.org/10.3390/pharmaceutics14030622Type
Articleae974a485f413a2113503eed53cd6c53
https://doi.org/10.3390/pharmaceutics14030622