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Spatiotemporal dynamics of doxorubicin elution from embolic beads within a microfluidic network

Spatiotemporal dynamics of doxorubicin elution from embolic beads within a microfluidic network
Spatiotemporal dynamics of doxorubicin elution from embolic beads within a microfluidic network
Anticancer treatment using embolic drug-eluting beads (DEBs) has shown multifarious advantages compared to systemic chemotherapy. However, there is a growing need for a better understanding of the physical parameters governing drug-elution from embolic devices under physiologically relevant fluidic conditions. In the present study, we investigated the spatiotemporal dynamics of doxorubicin hydrochloride elution from drug-loaded hydrogel embolic beads within a microfluidic device consisting of a network of interconnected microchannels which replicates the architectural properties of microvascular systems. Drug-elution has been investigated experimentally at a single-bead level, using in-house developed microscopy- and spectrofluorimetry-based methods. Results demonstrated that the kinetics of drug-elution and the amount of eluted drug strongly depended on the location of the embolic event within the embolised channel (e.g. fractional amount of eluted drug after 3 h was equal to ~ 0.2 and ~ 0.6 for completely-confined and partially-confined bead, respectively). Drug-elution from partially-confined bead showed a counterintuitive dependence on the local Reynolds number (and thus on the mean fluid velocity), as a result of dynamic changes in bead compressibility causing the displacement of the bead from the primary embolic site. Conversely, the kinetics of drug-elution from fully-confined bead was less affected by the local Reynolds number and bead displayed faster elution from the surface area exposed to the systemic flow, which was associated with the formation of fluid eddies nearby the bead post embolisation.
chemoembolisation, embolization, drug-elution, hydrogel bead, doxorubicin hydrochloride, microchannel network, microfluidics, hydrodynamics
0168-3659
62-75
Carugo, Dario
0a4be6cd-e309-4ed8-a620-20256ce01179
Capretto, Lorenzo
0f3586b5-1560-49c1-a76b-59e74ea600ef
Roy, Bibhas
ddd9f54b-7c0e-46eb-8e64-b2991562c5ea
Carboni, Michele
e3ef8207-6a01-4f2f-a498-37e8ac46a6eb
Caine, Marcus
b32f8e4b-3a11-47eb-9600-2eea10e87b8a
Lewis, Andrew L.
f604ae82-4d54-4f04-ac8f-e7bc6f1f832c
Hill, Martyn
0cda65c8-a70f-476f-b126-d2c4460a253e
Chakraborty, Suman
3683eef7-e86e-43a0-91f0-22826c9f4da6
Zhang, Xunli
d7cf1181-3276-4da1-9150-e212b333abb1
Carugo, Dario
0a4be6cd-e309-4ed8-a620-20256ce01179
Capretto, Lorenzo
0f3586b5-1560-49c1-a76b-59e74ea600ef
Roy, Bibhas
ddd9f54b-7c0e-46eb-8e64-b2991562c5ea
Carboni, Michele
e3ef8207-6a01-4f2f-a498-37e8ac46a6eb
Caine, Marcus
b32f8e4b-3a11-47eb-9600-2eea10e87b8a
Lewis, Andrew L.
f604ae82-4d54-4f04-ac8f-e7bc6f1f832c
Hill, Martyn
0cda65c8-a70f-476f-b126-d2c4460a253e
Chakraborty, Suman
3683eef7-e86e-43a0-91f0-22826c9f4da6
Zhang, Xunli
d7cf1181-3276-4da1-9150-e212b333abb1

Carugo, Dario, Capretto, Lorenzo, Roy, Bibhas, Carboni, Michele, Caine, Marcus, Lewis, Andrew L., Hill, Martyn, Chakraborty, Suman and Zhang, Xunli (2015) Spatiotemporal dynamics of doxorubicin elution from embolic beads within a microfluidic network. Journal of Controlled Release, 214, 62-75. (doi:10.1016/j.jconrel.2015.07.003). (PMID:26160306)

Record type: Article

Abstract

Anticancer treatment using embolic drug-eluting beads (DEBs) has shown multifarious advantages compared to systemic chemotherapy. However, there is a growing need for a better understanding of the physical parameters governing drug-elution from embolic devices under physiologically relevant fluidic conditions. In the present study, we investigated the spatiotemporal dynamics of doxorubicin hydrochloride elution from drug-loaded hydrogel embolic beads within a microfluidic device consisting of a network of interconnected microchannels which replicates the architectural properties of microvascular systems. Drug-elution has been investigated experimentally at a single-bead level, using in-house developed microscopy- and spectrofluorimetry-based methods. Results demonstrated that the kinetics of drug-elution and the amount of eluted drug strongly depended on the location of the embolic event within the embolised channel (e.g. fractional amount of eluted drug after 3 h was equal to ~ 0.2 and ~ 0.6 for completely-confined and partially-confined bead, respectively). Drug-elution from partially-confined bead showed a counterintuitive dependence on the local Reynolds number (and thus on the mean fluid velocity), as a result of dynamic changes in bead compressibility causing the displacement of the bead from the primary embolic site. Conversely, the kinetics of drug-elution from fully-confined bead was less affected by the local Reynolds number and bead displayed faster elution from the surface area exposed to the systemic flow, which was associated with the formation of fluid eddies nearby the bead post embolisation.

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More information

Accepted/In Press date: 1 July 2015
e-pub ahead of print date: 6 July 2015
Published date: 28 September 2015
Keywords: chemoembolisation, embolization, drug-elution, hydrogel bead, doxorubicin hydrochloride, microchannel network, microfluidics, hydrodynamics
Organisations: Bioengineering Group, Mechatronics

Identifiers

Local EPrints ID: 389477
URI: http://eprints.soton.ac.uk/id/eprint/389477
ISSN: 0168-3659
PURE UUID: 4c0044e6-9d8b-4480-b011-32a6802f1229
ORCID for Martyn Hill: ORCID iD orcid.org/0000-0001-6448-9448
ORCID for Xunli Zhang: ORCID iD orcid.org/0000-0002-4375-1571

Catalogue record

Date deposited: 08 Mar 2016 10:22
Last modified: 05 Nov 2019 02:06

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