A Preliminary Study of Drug Perfusion Enhancement by Microstreaming Induced by an Oscillating Microbubble
Microbubbbles incorporating ultrasound have been used to increase the efficacy of targeted drug delivery, because microstreaming induced by cavitating bubbles affects the drug perfusion into the target cells and tissues. In order to clarify the physical effects of microstreaming on drug perfusion into tissues, a preliminary experimental study of perfusion enhancement by a stably oscillating microbubble was performed. Microstreaming was induced by an oscillating bubble at 15 kHz, and perfusion of dye into an agar phantom was optically measured by histology on agar phantom. Surface color intensity and the penetration length of dye in the agar phantom were increased more than 70% and 30%, respectively, due to the microstreaming induced by an oscillating bubble. The mass of dye perfused into a tissue phantom for 30 s was increased about 80% in the phantom with an oscillating bubble. This preliminary experiment shows the physical effects of steady streaming by an oscillating bubble can enhance the drug perfusion into the tissues while minimizing the biological effects.
[1] K. Tachibana, T. Uchida, K. Ogawa, N. Yamashita, and K. Tamura, "Induction of cell membrane porosity by ultrasound," Lancet, vol. 353,
p. 1409, 1999.
[2] A. H. Mesiwala, L. Farell, H. J. Wenzel, D. L. Silvergelt, L. A. Crum, H. R. Winn, P. D. Mourad, "High intensity focused ultrasound selectively disrupts the blood-brain barrier in vivo," Ultrasound Med Biol., vol. 28,
pp. 389-400, 2002.
[3] K. E. Hichcock and C. K. Holland, "Ultrasound-assisted thrombolysis
for stroke therapy better thrombus break-up with bubbles," Stroke, vol.
41, pp. S50-S53, 2010.
[4] S. Datta, C. C. Coussios, L. E. McAdory, J. Tan, T. Porter, G. De
Courten-Myers, C. K. Holland, "Correlation of cavitation with
ultrasound enhancement of thrombolysis," Ultrasound Med Biol.,
vol.32, pp. 1257-1267, 2006.
[5] S. Datta, C. Coussios, A. Y. Ammi, T. D. Mast, De Courten-Myers, C.
K. Holland, "Ultrasound-enhanced thrombolysis using Definity® as a
cavitation nucleation agent," Ultrasound Med Biol., vol. 34, pp. 1421-
1433, 2008.
[6] A. F. Prokop, A. Soltani, and R. A. Roy, "Cavitational mechanisms in
ultrasound accelerated fibrinolysis," Ultrasound Med Biol., vol. 33, pp.
924 -933, 2007.
[7] K. E. Hitchcock, D. N. Caudell, J. T. Sutton, M. E. Klegerman, D. Vela,
G. J. Pyne-Geithman, T. Abruzzo, P. E. Cyr, Y. J. Geng, D. D. McPherson, and C. K. Holland, "Ultrasound-enhanced delivery of
targeted echogenic liposomes in a novel ex vivo mouse aorta model" J
Control Release., vol. 144, pp. 288-295, 2010.
[8] J. R. Lindner, J. Song, F. Xu, A. L. Klibanov, K. Singbartl, K. Ley et al.,
"Noninvasive ultrasound imaging of inflammation using microbubbles
targeted to activated leukocytes." Circulation, vol. 102, pp. 2745-50,2000.
[9] P. A. Schumann, J. P. Christiansen, R. M. Quigley, T. P. McCreery, R.
H. Sweitzer, E. C. Unger et al., "Targeted-microbubble binding
selectively to GPIIbIIIa receptors of platelet thrombi," Invest Radiol,
vol. 37, pp. 587-593, 2002.
[10] N. McDannold, N. Vykhodtseva, and K. Hynynen, "Blood-brain barrier disruption induced by focused ultrasound and circulating preformed microbubbles appears to be characterized by the mechanical index,"
Ultrasound Med. Biol., vol. 34, pp. 834-840, 2008.
[11] N. Vykhodtseva, N. McDannold, K. Hynynen, “Progress and problems
in the application of focused ultrasound for blood–brain barrier
disruption,” Ultrasonics, vol. 48 pp. 279–296, 2008.
[12] J. Wu, “Theoretical study on shear stress generated by microstreaming
surrounding contrast agents attached to living cells,” Ultrasound Med.
Biol., vol. 28, pp. 125–129, 2002.
[13] A. A. Doinkov and A. Bouakaz, “Theoretical investigation of shear
stress generated by a contrast microbubble on the cell membrane as a
mechanism for sonoporation,” J Acoust Soc Am, vol. 128, pp. 11-19,
2010.
[14] P. Marmottant and S. Hilgenfeldt, “Controlled deformation and lysis by
single oscillating bubbles,” Nature, vol. 423, pp. 153-156, 2003.
[15] J. Collis, R. Manasseh, P. Liovic, P. Th, A. Ooi, K. Petkovic_Duran, and
Y. Zhu, “Cavitation microstreaming and stress fields created by
microbubbles,” Ultrasonics, vol. 50, pp. 273–279, 2010.
[16] Z-J Chen, G. T. Gillies, W. C. Broaddus, S. S. Prabhu, H. Fillmore, R.
M. Mitchell, F. D. Corwin and P. P. Fatouros, “A realistic tissue
phantom for intraparenchymal infusion study,” J Neurosurg, 101, 314-
322, 2004.
[17] M. Kobayashi, S Sawada, N. Tanigawa, T. Senda and Y. Okuda, “Water
jet angioplasty- an experimental study,” Acta Radiologica, vol. 36, pp.
453-456, 1995.
[18] G.K Lewis and W. Olbricht, “A phantom feasibility study of acoustic
enhanced drug perfusion in neurological tissue,” Proc of IEEE Conf
LISSA, Ithaca, 2007, pp. 67-70.
[1] K. Tachibana, T. Uchida, K. Ogawa, N. Yamashita, and K. Tamura, "Induction of cell membrane porosity by ultrasound," Lancet, vol. 353,
p. 1409, 1999.
[2] A. H. Mesiwala, L. Farell, H. J. Wenzel, D. L. Silvergelt, L. A. Crum, H. R. Winn, P. D. Mourad, "High intensity focused ultrasound selectively disrupts the blood-brain barrier in vivo," Ultrasound Med Biol., vol. 28,
pp. 389-400, 2002.
[3] K. E. Hichcock and C. K. Holland, "Ultrasound-assisted thrombolysis
for stroke therapy better thrombus break-up with bubbles," Stroke, vol.
41, pp. S50-S53, 2010.
[4] S. Datta, C. C. Coussios, L. E. McAdory, J. Tan, T. Porter, G. De
Courten-Myers, C. K. Holland, "Correlation of cavitation with
ultrasound enhancement of thrombolysis," Ultrasound Med Biol.,
vol.32, pp. 1257-1267, 2006.
[5] S. Datta, C. Coussios, A. Y. Ammi, T. D. Mast, De Courten-Myers, C.
K. Holland, "Ultrasound-enhanced thrombolysis using Definity® as a
cavitation nucleation agent," Ultrasound Med Biol., vol. 34, pp. 1421-
1433, 2008.
[6] A. F. Prokop, A. Soltani, and R. A. Roy, "Cavitational mechanisms in
ultrasound accelerated fibrinolysis," Ultrasound Med Biol., vol. 33, pp.
924 -933, 2007.
[7] K. E. Hitchcock, D. N. Caudell, J. T. Sutton, M. E. Klegerman, D. Vela,
G. J. Pyne-Geithman, T. Abruzzo, P. E. Cyr, Y. J. Geng, D. D. McPherson, and C. K. Holland, "Ultrasound-enhanced delivery of
targeted echogenic liposomes in a novel ex vivo mouse aorta model" J
Control Release., vol. 144, pp. 288-295, 2010.
[8] J. R. Lindner, J. Song, F. Xu, A. L. Klibanov, K. Singbartl, K. Ley et al.,
"Noninvasive ultrasound imaging of inflammation using microbubbles
targeted to activated leukocytes." Circulation, vol. 102, pp. 2745-50,2000.
[9] P. A. Schumann, J. P. Christiansen, R. M. Quigley, T. P. McCreery, R.
H. Sweitzer, E. C. Unger et al., "Targeted-microbubble binding
selectively to GPIIbIIIa receptors of platelet thrombi," Invest Radiol,
vol. 37, pp. 587-593, 2002.
[10] N. McDannold, N. Vykhodtseva, and K. Hynynen, "Blood-brain barrier disruption induced by focused ultrasound and circulating preformed microbubbles appears to be characterized by the mechanical index,"
Ultrasound Med. Biol., vol. 34, pp. 834-840, 2008.
[11] N. Vykhodtseva, N. McDannold, K. Hynynen, “Progress and problems
in the application of focused ultrasound for blood–brain barrier
disruption,” Ultrasonics, vol. 48 pp. 279–296, 2008.
[12] J. Wu, “Theoretical study on shear stress generated by microstreaming
surrounding contrast agents attached to living cells,” Ultrasound Med.
Biol., vol. 28, pp. 125–129, 2002.
[13] A. A. Doinkov and A. Bouakaz, “Theoretical investigation of shear
stress generated by a contrast microbubble on the cell membrane as a
mechanism for sonoporation,” J Acoust Soc Am, vol. 128, pp. 11-19,
2010.
[14] P. Marmottant and S. Hilgenfeldt, “Controlled deformation and lysis by
single oscillating bubbles,” Nature, vol. 423, pp. 153-156, 2003.
[15] J. Collis, R. Manasseh, P. Liovic, P. Th, A. Ooi, K. Petkovic_Duran, and
Y. Zhu, “Cavitation microstreaming and stress fields created by
microbubbles,” Ultrasonics, vol. 50, pp. 273–279, 2010.
[16] Z-J Chen, G. T. Gillies, W. C. Broaddus, S. S. Prabhu, H. Fillmore, R.
M. Mitchell, F. D. Corwin and P. P. Fatouros, “A realistic tissue
phantom for intraparenchymal infusion study,” J Neurosurg, 101, 314-
322, 2004.
[17] M. Kobayashi, S Sawada, N. Tanigawa, T. Senda and Y. Okuda, “Water
jet angioplasty- an experimental study,” Acta Radiologica, vol. 36, pp.
453-456, 1995.
[18] G.K Lewis and W. Olbricht, “A phantom feasibility study of acoustic
enhanced drug perfusion in neurological tissue,” Proc of IEEE Conf
LISSA, Ithaca, 2007, pp. 67-70.
@article{"International Journal of Medical, Medicine and Health Sciences:50454", author = "Jin Sun Oh and Kyung Ho Lee and S ang Gug Chung and Kyehan Rhee", title = "A Preliminary Study of Drug Perfusion Enhancement by Microstreaming Induced by an Oscillating Microbubble", abstract = "Microbubbbles incorporating ultrasound have been used to increase the efficacy of targeted drug delivery, because microstreaming induced by cavitating bubbles affects the drug perfusion into the target cells and tissues. In order to clarify the physical effects of microstreaming on drug perfusion into tissues, a preliminary experimental study of perfusion enhancement by a stably oscillating microbubble was performed. Microstreaming was induced by an oscillating bubble at 15 kHz, and perfusion of dye into an agar phantom was optically measured by histology on agar phantom. Surface color intensity and the penetration length of dye in the agar phantom were increased more than 70% and 30%, respectively, due to the microstreaming induced by an oscillating bubble. The mass of dye perfused into a tissue phantom for 30 s was increased about 80% in the phantom with an oscillating bubble. This preliminary experiment shows the physical effects of steady streaming by an oscillating bubble can enhance the drug perfusion into the tissues while minimizing the biological effects.
", keywords = "Bubble, Mass Transfer, Microstreaming, Drug Delivery, Acoustic Wave.", volume = "6", number = "11", pages = "523-3", }
