Delivery of bevacizumab to atheromatous porcine carotid tissue using echogenic liposomes.
Ultrasound is both a valuable diagnostic tool and a promoter of beneficial tissue bioeffects for the treatment of cardiovascular disease. Vascular effects can be mediated by mechanical oscillations of circulating microbubbles that may also encapsulate and shield therapeutic agents in the bloodstream. Here, the effect of color-Doppler ultrasound exposure on bevacizumab-loaded liposome delivery into the vascular bed was assessed in atheromatous porcine carotids. Bevacizumab, an anti-angiogenic antibody to vascular endothelial growth factor (VEGF-A), was loaded into echogenic liposomes (BEV-ELIP) and confirmed to be immunoreactive. BEV-ELIP flowing within the lumen were exposed to color-Doppler ultrasound at three acoustic pressures for 3.5 min during treatment at physiologic temperature and fluid pressure. To confirm the presence of bubble activity, cavitation was detected within the lumen by a single-element passive cavitation detector. After treatment, the artery was fixed at physiologic pressure and subjected to immunohistochemical analysis to assess the penetration of bevacizumab within the carotid wall. The results suggest that other factors may more strongly influence the deposition of bevacizumab into carotid tissue than color-Doppler ultrasound and cavitation. In both sets of arteries, preferential accumulation of bevacizumab occurred in locations associated with atheroma progression and neointimal thickening: fibrous tissue, necrotic plaque and areas near macrophage infiltration. The delivery of bevacizumab to carotid vascular tissue correlated with the properties of the tissue bed, such as permeability, or affinity for growth-factor binding. Future investigations using this novel therapeutic strategy may focus on characterizing the spatial extent of delivery and bevacizumab colocalization with biochemical markers of atheroma.
a Biomedical Engineering Program, University of Cincinnati , Cincinnati , OH , USA.|f Philips Research North America , Cambridge , MA , USA.
J T
JT
Sutton
a Biomedical Engineering Program, University of Cincinnati , Cincinnati , OH , USA.|b College of Medicine, Internal Medicine, Division of Cardiovascular Diseases, University of Cincinnati , Cincinnati , OH , USA.
K J
KJ
Haworth
c Department of Pathology , Cincinnati Children's Hospital Medical Center , Cincinnati , OH , USA.|d College of Medicine, Pathology and Laboratory Medicine, University of Cincinnati , Cincinnati , OH , USA.
S K
SK
Shanmukhappa
e Department of Internal Medicine , University of Texas Health Science Center , Houston , TX , USA , and.
M R
MR
Moody
e Department of Internal Medicine , University of Texas Health Science Center , Houston , TX , USA , and.
M E
ME
Klegerman
a Biomedical Engineering Program, University of Cincinnati , Cincinnati , OH , USA.
J K
JK
Griffin
a Biomedical Engineering Program, University of Cincinnati , Cincinnati , OH , USA.
D M
DM
Patton
e Department of Internal Medicine , University of Texas Health Science Center , Houston , TX , USA , and.
D D
DD
McPherson
a Biomedical Engineering Program, University of Cincinnati , Cincinnati , OH , USA.|b College of Medicine, Internal Medicine, Division of Cardiovascular Diseases, University of Cincinnati , Cincinnati , OH , USA.
C K
CK
Holland
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D013552:Swine; D014465:Ultrasonics / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D008081:Liposomes; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
Ultrasound; atherosclerosis; bevacizumab; cavitation; liposomes
Circ Res. 2009 Mar 13;104(5):679-87
19168443
Ultrasound Med Biol. 2016 Feb;42(2):518-27
26547633
Ultrasound Med Biol. 2010 Jun;36(6):916-24
20447757
J Control Release. 2012 Aug 20;162(1):134-42
22709590
J Acoust Soc Am. 2009 Dec;126(6):3071-83
20000921
J Liposome Res. 2016;26(1):47-56
25865025
Acta Physiol (Oxf). 2015 Mar;213(3):539-53
25515699
Expert Opin Drug Discov. 2012 Aug;7(8):723-43
22716277
Am J Physiol Heart Circ Physiol. 2010 Feb;298(2):H295-305
19940078
J Am Coll Cardiol. 2009 Dec 1;54(23):2129-38
19942084
Nat Med. 2004 Feb;10(2):145-7
14745444
J Control Release. 2010 Feb 25;142(1):31-9
19818371
Atherosclerosis. 2007 Jun;192(2):246-52
16919638
J Control Release. 2015 Jun 10;207 :101-11
25862513
Target Oncol. 2015 Dec;10 (4):487-99
25922090
J Mol Neurosci. 2012 Mar;46(3):677-87
21861133
Adv Drug Deliv Rev. 2008 Jun 30;60(10):1167-76
18479776
IEEE Trans Biomed Eng. 2015 May;62(5):1293-304
25546853
Ultrasound Med Biol. 2006 Sep;32(9):1399-409
16965980
FASEB J. 2010 Dec;24(12):4711-21
20671107
IEEE Trans Med Imaging. 2015 Jun;34(6):1270-81
25546857
J Pathol. 1999 Jun;188(2):189-96
10398163
J Control Release. 2014 Aug 10;187:39-49
24852099
Circulation. 2014 Jan 21;129(3):e28-e292
24352519
Adv Drug Deliv Rev. 2014 Jun;72:94-109
24462453
Ultrasound Med Biol. 2012 Oct;38(10):1716-25
22818878
J Acoust Soc Am. 2012 Jul;132(1):544-53
22779500
Annu Rev Biomed Eng. 2003;5:79-118
12651738
Stroke. 1997 Mar;28(3):665-71
9056629
J Biol Chem. 2003 Apr 11;278(15):12605-8
12538598
Dis Markers. 2002;18(5-6):293-311
14646042
J Histochem Cytochem. 2008 Apr;56(4):313-28
18158282
Expert Opin Drug Deliv. 2013 May;10(5):573-92
23448121
Phys Med Biol. 2013 Jan 7;58(1):127-44
23221109
Arterioscler Thromb Vasc Biol. 2005 Oct;25(10):2054-61
16037567
JAMA. 2005 Mar 23;293(12 ):1509-13
15784876
Isr J Med Sci. 1969 Jul-Aug;5(4):639-43
4980551
N Engl J Med. 2003 Jul 31;349(5):427-34
12890841
Arterioscler Thromb Vasc Biol. 2000 Jun;20(6):1622-9
10845881
Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4736-41
12682294
J Pathol. 2009 May;218(1):7-29
19309025
Thromb Res. 2012 Oct;130(4):629-35
22133272
Int J Nanomedicine. 2014 Oct 06;9:4671-83
25336947
J Control Release. 2013 Jul 10;169(1-2):103-11
23603615
J Control Release. 2006 May 15;112(2):149-55
16556469
Cardiovasc Res. 2007 Sep 1;75(4):649-58
17631284
J Biomech. 2014 Mar 3;47(4):847-58
24485514
Circulation. 2011 Mar 1;123(8):933-44
21262990
Ultrasound Med Biol. 2002 Mar;28(3):339-48
11978414
Invest Radiol. 2010 Oct;45(10 ):685-91
20733507
J Control Release. 2010 Jun 15;144(3):288-95
20202474
Ultrasound Med Biol. 2004 Jul;30(7):979-89
15313330
J Control Release. 2013 Nov 28;172(1):274-80
24008151
Med Res Rev. 2006 Jul;26(4):483-530
16652370
Phys Med Biol. 2015 Jan 21;60(2):785-806
25564961
Oncologist. 2007 Apr;12 (4):465-77
17470689
Ultrasonics. 2008 Aug;48(4):279-96
18511095
Anal Quant Cytol Histol. 2001 Aug;23(4):291-9
11531144
Circulation. 1992 Jan;85(1):391-405
1728483