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In vitro ultrasound-mediated leakage from phospholipid vesicles
Please use this identifier to cite or link to this item:
http://hdl.handle.net/1860/1643
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| 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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