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Contrast agent-free sonoporation: the use of an ultrasonic standing wave microfluidic system for the delivery of pharmaceutical agents

Contrast agent-free sonoporation: the use of an ultrasonic standing wave microfluidic system for the delivery of pharmaceutical agents
Contrast agent-free sonoporation: the use of an ultrasonic standing wave microfluidic system for the delivery of pharmaceutical agents
Sonoporation is a useful biophysical mechanism for facilitating the transmembrane delivery of therapeutic agents from the extracellular to the intracellular milieu. Conventionally, sonoporation is carried out in the presence of ultrasound contrast agents, which are known to greatly enhance transient poration of biological cell membranes. However, in vivo contrast agents have been observed to induce capillary rupture and haemorrhage due to endothelial cell damage and to greatly increase the potential for cell lysis in vitro. Here, we demonstrate sonoporation of cardiac myoblasts in the absence of contrast agent (CA-free sonoporation) using a low-cost ultrasound-microfluidic device. Within this device an ultrasonic standing wave was generated, allowing control over the position of the cells and the strength of the acoustic radiation forces. Real-time single-cell analysis and retrospective postsonication analysis of insonated cardiac myoblasts showed that CA-free sonoporation induced transmembrane transfer of fluorescent probes (CMFDA and FITC-dextran) and that different mechanisms potentially contribute to membrane poration in the presence of an ultrasonic wave. Additionally, to the best of our knowledge, we have shown for the first time that sonoporation induces increased cell cytotoxicity as a consequence of CA-free ultrasound-facilitated uptake of pharmaceutical agents (doxorubicin, luteolin, and apigenin). The US-microfluidic device designed here provides an in vitro alternative to expensive and controversial in vivo models used for early stage drug discovery, and drug delivery programs and toxicity measurements.
bioacoustics, biomedical ultrasonics, biomembrane transport, drug delivery systems
1932-1058
044108-[15pp]
Carugo, Dario
0a4be6cd-e309-4ed8-a620-20256ce01179
Ankrett, Dyan N.
22d8eb6d-70db-4b47-9587-c4d048cd34b7
Glynne-Jones, Peter
6ca3fcbc-14db-4af9-83e2-cf7c8b91ef0d
Capretto, Lorenzo
0f3586b5-1560-49c1-a76b-59e74ea600ef
Boltryk, Rosemary J.
0452b21c-a758-4d4a-925b-1511d9296d62
Zhang, Xunli
d7cf1181-3276-4da1-9150-e212b333abb1
Townsend, Paul A.
a2680443-664e-46d0-b4dd-97456ba810db
Hill, Martyn
0cda65c8-a70f-476f-b126-d2c4460a253e
Carugo, Dario
0a4be6cd-e309-4ed8-a620-20256ce01179
Ankrett, Dyan N.
22d8eb6d-70db-4b47-9587-c4d048cd34b7
Glynne-Jones, Peter
6ca3fcbc-14db-4af9-83e2-cf7c8b91ef0d
Capretto, Lorenzo
0f3586b5-1560-49c1-a76b-59e74ea600ef
Boltryk, Rosemary J.
0452b21c-a758-4d4a-925b-1511d9296d62
Zhang, Xunli
d7cf1181-3276-4da1-9150-e212b333abb1
Townsend, Paul A.
a2680443-664e-46d0-b4dd-97456ba810db
Hill, Martyn
0cda65c8-a70f-476f-b126-d2c4460a253e

Carugo, Dario, Ankrett, Dyan N., Glynne-Jones, Peter, Capretto, Lorenzo, Boltryk, Rosemary J., Zhang, Xunli, Townsend, Paul A. and Hill, Martyn (2011) Contrast agent-free sonoporation: the use of an ultrasonic standing wave microfluidic system for the delivery of pharmaceutical agents. Biomicrofluidics, 5 (4), 044108-[15pp]. (doi:10.1063/1.3660352).

Record type: Article

Abstract

Sonoporation is a useful biophysical mechanism for facilitating the transmembrane delivery of therapeutic agents from the extracellular to the intracellular milieu. Conventionally, sonoporation is carried out in the presence of ultrasound contrast agents, which are known to greatly enhance transient poration of biological cell membranes. However, in vivo contrast agents have been observed to induce capillary rupture and haemorrhage due to endothelial cell damage and to greatly increase the potential for cell lysis in vitro. Here, we demonstrate sonoporation of cardiac myoblasts in the absence of contrast agent (CA-free sonoporation) using a low-cost ultrasound-microfluidic device. Within this device an ultrasonic standing wave was generated, allowing control over the position of the cells and the strength of the acoustic radiation forces. Real-time single-cell analysis and retrospective postsonication analysis of insonated cardiac myoblasts showed that CA-free sonoporation induced transmembrane transfer of fluorescent probes (CMFDA and FITC-dextran) and that different mechanisms potentially contribute to membrane poration in the presence of an ultrasonic wave. Additionally, to the best of our knowledge, we have shown for the first time that sonoporation induces increased cell cytotoxicity as a consequence of CA-free ultrasound-facilitated uptake of pharmaceutical agents (doxorubicin, luteolin, and apigenin). The US-microfluidic device designed here provides an in vitro alternative to expensive and controversial in vivo models used for early stage drug discovery, and drug delivery programs and toxicity measurements.

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More information

e-pub ahead of print date: 15 November 2011
Published date: 2011
Keywords: bioacoustics, biomedical ultrasonics, biomembrane transport, drug delivery systems
Organisations: Cancer Sciences, Bioengineering Group, Mechatronics

Identifiers

Local EPrints ID: 203735
URI: https://eprints.soton.ac.uk/id/eprint/203735
ISSN: 1932-1058
PURE UUID: cd480d6e-a81c-4ed4-8961-b82e9db28c28
ORCID for Peter Glynne-Jones: ORCID iD orcid.org/0000-0001-5684-3953
ORCID for Martyn Hill: ORCID iD orcid.org/0000-0001-6448-9448

Catalogue record

Date deposited: 21 Nov 2011 11:38
Last modified: 06 Jun 2018 13:12

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