Predicting pharmacokinetic behaviour of drug release from drug-eluting embolization beads using in vitro elution methods

Alice Hagan, Marcus Caine, Cara Press, Wendy Macfarlane, Gary Phillips, Andrew Lloyd, Peter Czuczman, Hugh Kilpatrick, Zainab Bascal, Yiqing Tang, Pedro Garcia, Andrew Lewis

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Drug-eluting Embolic Bead - Transarterial Chemoembolisation (DEB-TACE) is a minimally invasive embolising treatment for liver tumours that allows local release of chemotherapeutic drugs via ion exchange, following delivery into hepatic arterial vasculature. Thus far, no single in vitro model has been able to accurately predict the complete kinetics of drug release from DEB, due to heterogeneity of rate-controlling mechanisms throughout the process of DEB delivery. In this study, we describe two in vitro models capable of distinguishing between early phase and late phase drug release by mimicking in vivo features of each phase. First, a vascular flow system (VFS) was used to simulate the early phase by delivering DEB into a silicon vascular cast under high pulsatile flow. This yielded a burst release profile of drugs from DEB which related to the dose adjusted Cmax observed in pharmacokinetic plasma profiles from a preclinical swine model. Second, an open loop flow-through cell system was used to model late phase drug release by packing beads in a column with an ultra-low flow rate. DEB loaded with doxorubicin, irinotecan and vandetanib showed differential drug release rates due to their varying chemical properties and unique drug-bead interactions. Using more representative in vitro models to map discrete phases of DEB drug release will provide a better capability to predict the pharmacokinetics of developmental formulations, which has implications for treatment safety and efficacy.
Original languageEnglish
Article number104943
Pages (from-to)1-24
Number of pages24
JournalEuropean Journal of Pharmaceutical Sciences
Volume136
DOIs
Publication statusPublished - 29 May 2019

Fingerprint

Pharmacokinetics
Pharmaceutical Preparations
irinotecan
Blood Vessels
Pulsatile Flow
Ion Exchange
Liver
Silicon
Drug Liberation
In Vitro Techniques
Drug Interactions
Doxorubicin
Swine
Safety
Neoplasms

Bibliographical note

© 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/)

Keywords

  • IVIVC
  • Drug-eluting beads
  • Chemoembolisation
  • Vandetanib
  • Drug delivery

Cite this

Hagan, Alice ; Caine, Marcus ; Press, Cara ; Macfarlane, Wendy ; Phillips, Gary ; Lloyd, Andrew ; Czuczman, Peter ; Kilpatrick, Hugh ; Bascal, Zainab ; Tang, Yiqing ; Garcia, Pedro ; Lewis, Andrew. / Predicting pharmacokinetic behaviour of drug release from drug-eluting embolization beads using in vitro elution methods. In: European Journal of Pharmaceutical Sciences. 2019 ; Vol. 136. pp. 1-24.
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Predicting pharmacokinetic behaviour of drug release from drug-eluting embolization beads using in vitro elution methods. / Hagan, Alice; Caine, Marcus; Press, Cara; Macfarlane, Wendy; Phillips, Gary; Lloyd, Andrew; Czuczman, Peter; Kilpatrick, Hugh; Bascal, Zainab; Tang, Yiqing; Garcia, Pedro; Lewis, Andrew.

In: European Journal of Pharmaceutical Sciences, Vol. 136, 104943, 29.05.2019, p. 1-24.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Hagan, Alice

AU - Caine, Marcus

AU - Press, Cara

AU - Macfarlane, Wendy

AU - Phillips, Gary

AU - Lloyd, Andrew

AU - Czuczman, Peter

AU - Kilpatrick, Hugh

AU - Bascal, Zainab

AU - Tang, Yiqing

AU - Garcia, Pedro

AU - Lewis, Andrew

N1 - © 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/)

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AB - Drug-eluting Embolic Bead - Transarterial Chemoembolisation (DEB-TACE) is a minimally invasive embolising treatment for liver tumours that allows local release of chemotherapeutic drugs via ion exchange, following delivery into hepatic arterial vasculature. Thus far, no single in vitro model has been able to accurately predict the complete kinetics of drug release from DEB, due to heterogeneity of rate-controlling mechanisms throughout the process of DEB delivery. In this study, we describe two in vitro models capable of distinguishing between early phase and late phase drug release by mimicking in vivo features of each phase. First, a vascular flow system (VFS) was used to simulate the early phase by delivering DEB into a silicon vascular cast under high pulsatile flow. This yielded a burst release profile of drugs from DEB which related to the dose adjusted Cmax observed in pharmacokinetic plasma profiles from a preclinical swine model. Second, an open loop flow-through cell system was used to model late phase drug release by packing beads in a column with an ultra-low flow rate. DEB loaded with doxorubicin, irinotecan and vandetanib showed differential drug release rates due to their varying chemical properties and unique drug-bead interactions. Using more representative in vitro models to map discrete phases of DEB drug release will provide a better capability to predict the pharmacokinetics of developmental formulations, which has implications for treatment safety and efficacy.

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