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

Wenbo Zhan* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number69
JournalPharmaceutics
Volume12
Issue number1
DOIs
Publication statusPublished - 15 Jan 2020

Fingerprint

Microbubbles
Blood-Brain Barrier
Brain Neoplasms
Liposomes
Pharmaceutical Preparations
Doxorubicin
Injections
Sonication
Therapeutics
Drug Liberation

Keywords

  • blood brain barrier disruption
  • brain tumour
  • drug transport
  • focused ultrasound
  • liposome-mediated delivery
  • mathematical model
  • Drug transport
  • Brain tumour
  • Liposome-mediated delivery
  • Focused ultrasound
  • Blood-brain barrier disruption
  • Mathematical model

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

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title = "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",
abstract = "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.",
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author = "Wenbo Zhan",
note = "Funding: This research received no external funding. Acknowledgments: The author would like to acknowledge the supports of the Imperial College London Central Library and the Maxwell Compute Cluster funded by the University of Aberdeen.",
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