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


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).

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Description/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.

Item Type: Article
ISSNs: 1932-1058 (print)
1932-1058 (electronic)
Keywords: bioacoustics, biomedical ultrasonics, biomembrane transport, drug delivery systems
Subjects: Q Science > QR Microbiology
Divisions: Faculty of Engineering and the Environment > Engineering Sciences > Bioengineering Research Group
Faculty of Engineering and the Environment > Engineering Sciences > Electro-Mechanical Research Group
Faculty of Medicine > Cancer Sciences
ePrint ID: 203735
Date Deposited: 21 Nov 2011 11:38
Last Modified: 14 Apr 2014 11:07
Projects:
Electronic Sonotweezers: Particle Manipulation with Ultrasonic Arrays
Funded by: EPSRC (EP/G012075/1)
Led by: Martyn Hill
1 June 2009 to 17 November 2013
URI: http://eprints.soton.ac.uk/id/eprint/203735

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