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Open AccessArticle

Effects of Focused-Ultrasound-and-Microbubble-Induced Blood-Brain Barrier Disruption on Drug Transport under Liposome-Mediated Delivery in Brain Tumour: A Pilot Numerical Simulation Study

by Wenbo Zhan 1,2
1
School of Engineering, University of Aberdeen, Aberdeen AB24 3UE, UK
2
Department of Mechanical Engineering, Imperial College London, London SW7 2AZ, UK
Pharmaceutics 2020, 12(1), 69; https://doi.org/10.3390/pharmaceutics12010069 (registering DOI)
Received: 10 November 2019 / Revised: 17 December 2019 / Accepted: 9 January 2020 / Published: 15 January 2020
(This article belongs to the Special Issue Biocompatible Materials in Drug Delivery System in Oncology)
Focused ultrasound (FUS) coupled with microbubbles (MB) has been found to be a promising approach to disrupt the blood-brain barrier (BBB). However, how this disruption affects drug transport remains unclear. In this study, drug transport in combination therapy of liposomes and FUS-MB-induced BBB disruption (BBBD) was investigated based on a multiphysics model. A realistic 3D brain tumour model extracted from MR images was applied. The results demonstrated the advantage of liposomes compared to free doxorubicin injection in further improving treatment when the BBB is opened under the same delivery conditions using burst sonication. This improvement was mainly due to the BBBD-enhanced transvascular transport of free doxorubicin and the sustainable supply of the drug by long-circulating liposomes. Treatment efficacy can be improved in different ways. Disrupting the BBB simultaneously with liposome bolus injection enables more free drug molecules to cross the vessel wall, while prolonging the BBBD duration could accelerate liposome transvascular transport for more effective drug release. However, the drug release rate needs to be well controlled to balance the trade-off among drug release, transvascular exchange and elimination. The results obtained in this study could provide suggestions for the future optimisation of this FUS-MB–liposome combination therapy against brain cancer. View Full-Text
Keywords: blood-brain barrier disruption; brain tumour; drug transport; focused ultrasound; liposome-mediated delivery; mathematical model blood-brain barrier disruption; brain tumour; drug transport; focused ultrasound; liposome-mediated delivery; mathematical model
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MDPI and ACS Style

Zhan, W. Effects of Focused-Ultrasound-and-Microbubble-Induced Blood-Brain Barrier Disruption on Drug Transport under Liposome-Mediated Delivery in Brain Tumour: A Pilot Numerical Simulation Study. Pharmaceutics 2020, 12, 69.

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