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Please use this identifier to cite or link to this item: http://hdl.handle.net/1860/1643

Title: In vitro ultrasound-mediated leakage from phospholipid vesicles
Authors: Pong, Mona
Umchid, Sumet
Guarino, Andrew Joseph
Lewin, Peter A.
Litniewski, Jerzy
Nowicki, Andrzej
Wrenn, Steven P.
Keywords: Ultrasound exposure;Therapeutic ultrasound;Membrane permeability;Giant vesicles;PEG2000
Issue Date: 2006
Publisher: Elsevier Science B.V.
Citation: Ultrasonics, 45(1-4): pp. 133-145.
Abstract: Interest in using ultrasound energy in wound management and intracellular drug delivery has been growing rapidly. Development and treatment optimization of such non-diagnostic applications requires a fundamental understanding of interactions between the acoustic wave and phospholipid membranes, be they cell membranes or liposome bilayers. This work investigates the changes in membrane permeation (leakage mimicking drug release) in vitro during exposure to ultrasound applied in two frequency ranges: “conventional” (1 MHz and 1.6 MHz) therapeutic ultrasound range and low (20 kHz) frequency range. Phospholipids vesicles were used as controllable biological membrane models. The membrane properties were modified by changes in vesicle dimensions and incorporation of poly(ethylene glycol) i.e. PEGylated lipids. Egg phosphatidylcholine vesicles with 5 mol % PEG were prepared with sizes ranging from 100 nm to 1 μm. Leakage was quantified in terms of temporal fluorescence intensity changes observed during carefully controlled ultrasound ON/OFF time intervals. Custom-built transducers operating at frequencies of 1.6 MHz (focused) and 1.0 MHz (unfocused) were used, the Ispta of which were 46.9 W/cm2 and 3.0 W/cm2, respectively. A commercial 20 kHz, point-source, continuous wave transducer with an Ispta of 0.13 W/cm2 was also used for comparative purposes. Whereas complete leakage was obtained for all vesicle sizes at 20 kHz, no leakage was observed for vesicles smaller than 100 nm in diameter at 1.6 or 1.0 MHz. However, introducing leakage at the higher frequencies became feasible when larger (greater than 300 nm) vesicles were used, and the extent of leakage correlated well with vesicle sizes between 100 nm and 1 μm. This observation suggests that physico-chemical membrane properties play a crucial role in ultrasound mediated membrane permeation and that low frequency (tens of kilohertz) ultrasound 3 exposure is more effective in introducing permeability change than the “conventional” (1 MHz) therapeutic one. The experimental data also indicate that the leakage level is controlled by the exposure time. The results of this work might be helpful to optimize acoustic field and membrane parameters for gene or drug delivery. The outcome of this work might also be useful in wound management.
URI: http://dx.doi.org/10.1016/j.ultras.2006.07.021
http://hdl.handle.net/1860/1643
Appears in Collections:Faculty Research and Publications (CBE)

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