Systemic targeted delivery of antisense with perflourobutane gas microbubble carrier reduced neointimal formation in the porcine coronary restenosis model

Nicholas N. Kipshidze; Thomas R. Porter; George Dangas; Hamid Yazdi; Fermin Tio; Feng Xie; David Hellinga; Jana Fournadjiev; Roswitha Wolfram; Rufus Seabron; Ron Waksman; Alexander Abizaid; Gary Roubin; Sriram Iyer; Martin B. Leon; Jeffrey W. Moses; Patrick Iversen

doi:10.1016/S1522-1865(03)00184-7

Systemic targeted delivery of antisense with perflourobutane gas microbubble carrier reduced neointimal formation in the porcine coronary restenosis model

Nicholas N. Kipshidze, Thomas R. Porter, George Dangas, Hamid Yazdi, Fermin Tio, Feng Xie, David Hellinga, Jana Fournadjiev, Roswitha Wolfram, Rufus Seabron, Ron Waksman, Alexander Abizaid, Gary Roubin, Sriram Iyer, Martin B. Leon, Jeffrey W. Moses, Patrick Iversen

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Hypothesis: The antisense phosphorodiamidate morpholino oligomer (PMO), AVI-4126, has been effective in reducing neointimal formation in animal models following delivery by pluronic gels, local delivery catheters and coated stents. Greater flexibility of repeated-dosage regimens and reduced procedure complexity may be provided by systemic injection of AVI-4126 bound to perfluorobutane gas microbubble carriers. The purpose of this study was to investigate the effects of perfluorocarbon gas microbubble carrier (PGMC)-based systemic delivery of AVI-4126 on expression of the c-myc in vascular tissue and restenosis after stent implantation. Methods: Seven pigs underwent stent implantation (3 stents/animal). Five pigs received IV injection of PGMC and 2 mg of AVI-4126 (AVI BioPharma). Two served as control. Four hours postprocedure, 3 pigs were sacrificed and stented segments analyzed by high-performance liquid chromatography (HPLC) and Western blot. In chronic experiments, 4 pigs (12 stent sites) were sacrificed at 28 days. Results: HPLC analysis of plasma samples of treated animals showed minimal presence of AVI-4126. HPLC of the treated arteries demonstrated easily detected concentrations of AVI-4126. Western blot analysis of the stented vessels demonstrated modest inhibition of c-myc. Morphometry showed that the neointimal area was significantly reduced in the AVI-4126/PGMC group compared with control (2.63±1.99 vs. 4.77±.1.71 mm², respectively, P<.05). Conclusion: In the porcine coronary stent model, systemic targeted delivery of AVI-4126 using PGMC carrier significantly inhibited neointimal formation.

Original language	English (US)
Pages (from-to)	152-159
Number of pages	8
Journal	Cardiovascular Radiation Medicine
Volume	4
Issue number	3
DOIs	https://doi.org/10.1016/S1522-1865(03)00184-7
State	Published - 2003
Externally published	Yes

Keywords

Antisense
Nanoparticles
Restenosis
Stents

ASJC Scopus subject areas

Surgery
Molecular Medicine
Cardiology and Cardiovascular Medicine

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10.1016/S1522-1865(03)00184-7

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Kipshidze, N. N., Porter, T. R., Dangas, G., Yazdi, H., Tio, F., Xie, F., Hellinga, D., Fournadjiev, J., Wolfram, R., Seabron, R., Waksman, R., Abizaid, A., Roubin, G., Iyer, S., Leon, M. B., Moses, J. W., & Iversen, P. (2003). Systemic targeted delivery of antisense with perflourobutane gas microbubble carrier reduced neointimal formation in the porcine coronary restenosis model. Cardiovascular Radiation Medicine, 4(3), 152-159. https://doi.org/10.1016/S1522-1865(03)00184-7

Kipshidze, NN, Porter, TR, Dangas, G, Yazdi, H, Tio, F, Xie, F, Hellinga, D, Fournadjiev, J, Wolfram, R, Seabron, R, Waksman, R, Abizaid, A, Roubin, G, Iyer, S, Leon, MB, Moses, JW & Iversen, P 2003, 'Systemic targeted delivery of antisense with perflourobutane gas microbubble carrier reduced neointimal formation in the porcine coronary restenosis model', Cardiovascular Radiation Medicine, vol. 4, no. 3, pp. 152-159. https://doi.org/10.1016/S1522-1865(03)00184-7

@article{db147d9170f847869cc00c47b1b9a7f3,

title = "Systemic targeted delivery of antisense with perflourobutane gas microbubble carrier reduced neointimal formation in the porcine coronary restenosis model",

abstract = "Hypothesis: The antisense phosphorodiamidate morpholino oligomer (PMO), AVI-4126, has been effective in reducing neointimal formation in animal models following delivery by pluronic gels, local delivery catheters and coated stents. Greater flexibility of repeated-dosage regimens and reduced procedure complexity may be provided by systemic injection of AVI-4126 bound to perfluorobutane gas microbubble carriers. The purpose of this study was to investigate the effects of perfluorocarbon gas microbubble carrier (PGMC)-based systemic delivery of AVI-4126 on expression of the c-myc in vascular tissue and restenosis after stent implantation. Methods: Seven pigs underwent stent implantation (3 stents/animal). Five pigs received IV injection of PGMC and 2 mg of AVI-4126 (AVI BioPharma). Two served as control. Four hours postprocedure, 3 pigs were sacrificed and stented segments analyzed by high-performance liquid chromatography (HPLC) and Western blot. In chronic experiments, 4 pigs (12 stent sites) were sacrificed at 28 days. Results: HPLC analysis of plasma samples of treated animals showed minimal presence of AVI-4126. HPLC of the treated arteries demonstrated easily detected concentrations of AVI-4126. Western blot analysis of the stented vessels demonstrated modest inhibition of c-myc. Morphometry showed that the neointimal area was significantly reduced in the AVI-4126/PGMC group compared with control (2.63±1.99 vs. 4.77±.1.71 mm2, respectively, P<.05). Conclusion: In the porcine coronary stent model, systemic targeted delivery of AVI-4126 using PGMC carrier significantly inhibited neointimal formation.",

keywords = "Antisense, Nanoparticles, Restenosis, Stents",

author = "Kipshidze, {Nicholas N.} and Porter, {Thomas R.} and George Dangas and Hamid Yazdi and Fermin Tio and Feng Xie and David Hellinga and Jana Fournadjiev and Roswitha Wolfram and Rufus Seabron and Ron Waksman and Alexander Abizaid and Gary Roubin and Sriram Iyer and Leon, {Martin B.} and Moses, {Jeffrey W.} and Patrick Iversen",

note = "Funding Information: These studies were supported in part by AVI BioPharma (Portland, OR), Cook Cardiology (Broomfield, CO), Leon Hess research grant at Lenox Hill Hospital (New York, NY), and Cardiovascular Research Foundation, New York, NY.",

year = "2003",

doi = "10.1016/S1522-1865(03)00184-7",

language = "English (US)",

volume = "4",

pages = "152--159",

journal = "Cardiovascular Revascularization Medicine",

issn = "1553-8389",

publisher = "Elsevier Inc.",

number = "3",

}

TY - JOUR

T1 - Systemic targeted delivery of antisense with perflourobutane gas microbubble carrier reduced neointimal formation in the porcine coronary restenosis model

AU - Kipshidze, Nicholas N.

AU - Porter, Thomas R.

AU - Dangas, George

AU - Yazdi, Hamid

AU - Tio, Fermin

AU - Xie, Feng

AU - Hellinga, David

AU - Fournadjiev, Jana

AU - Wolfram, Roswitha

AU - Seabron, Rufus

AU - Waksman, Ron

AU - Abizaid, Alexander

AU - Roubin, Gary

AU - Iyer, Sriram

AU - Leon, Martin B.

AU - Moses, Jeffrey W.

AU - Iversen, Patrick

N1 - Funding Information: These studies were supported in part by AVI BioPharma (Portland, OR), Cook Cardiology (Broomfield, CO), Leon Hess research grant at Lenox Hill Hospital (New York, NY), and Cardiovascular Research Foundation, New York, NY.

PY - 2003

Y1 - 2003

N2 - Hypothesis: The antisense phosphorodiamidate morpholino oligomer (PMO), AVI-4126, has been effective in reducing neointimal formation in animal models following delivery by pluronic gels, local delivery catheters and coated stents. Greater flexibility of repeated-dosage regimens and reduced procedure complexity may be provided by systemic injection of AVI-4126 bound to perfluorobutane gas microbubble carriers. The purpose of this study was to investigate the effects of perfluorocarbon gas microbubble carrier (PGMC)-based systemic delivery of AVI-4126 on expression of the c-myc in vascular tissue and restenosis after stent implantation. Methods: Seven pigs underwent stent implantation (3 stents/animal). Five pigs received IV injection of PGMC and 2 mg of AVI-4126 (AVI BioPharma). Two served as control. Four hours postprocedure, 3 pigs were sacrificed and stented segments analyzed by high-performance liquid chromatography (HPLC) and Western blot. In chronic experiments, 4 pigs (12 stent sites) were sacrificed at 28 days. Results: HPLC analysis of plasma samples of treated animals showed minimal presence of AVI-4126. HPLC of the treated arteries demonstrated easily detected concentrations of AVI-4126. Western blot analysis of the stented vessels demonstrated modest inhibition of c-myc. Morphometry showed that the neointimal area was significantly reduced in the AVI-4126/PGMC group compared with control (2.63±1.99 vs. 4.77±.1.71 mm2, respectively, P<.05). Conclusion: In the porcine coronary stent model, systemic targeted delivery of AVI-4126 using PGMC carrier significantly inhibited neointimal formation.

AB - Hypothesis: The antisense phosphorodiamidate morpholino oligomer (PMO), AVI-4126, has been effective in reducing neointimal formation in animal models following delivery by pluronic gels, local delivery catheters and coated stents. Greater flexibility of repeated-dosage regimens and reduced procedure complexity may be provided by systemic injection of AVI-4126 bound to perfluorobutane gas microbubble carriers. The purpose of this study was to investigate the effects of perfluorocarbon gas microbubble carrier (PGMC)-based systemic delivery of AVI-4126 on expression of the c-myc in vascular tissue and restenosis after stent implantation. Methods: Seven pigs underwent stent implantation (3 stents/animal). Five pigs received IV injection of PGMC and 2 mg of AVI-4126 (AVI BioPharma). Two served as control. Four hours postprocedure, 3 pigs were sacrificed and stented segments analyzed by high-performance liquid chromatography (HPLC) and Western blot. In chronic experiments, 4 pigs (12 stent sites) were sacrificed at 28 days. Results: HPLC analysis of plasma samples of treated animals showed minimal presence of AVI-4126. HPLC of the treated arteries demonstrated easily detected concentrations of AVI-4126. Western blot analysis of the stented vessels demonstrated modest inhibition of c-myc. Morphometry showed that the neointimal area was significantly reduced in the AVI-4126/PGMC group compared with control (2.63±1.99 vs. 4.77±.1.71 mm2, respectively, P<.05). Conclusion: In the porcine coronary stent model, systemic targeted delivery of AVI-4126 using PGMC carrier significantly inhibited neointimal formation.

KW - Antisense

KW - Nanoparticles

KW - Restenosis

KW - Stents

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U2 - 10.1016/S1522-1865(03)00184-7

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AN - SCOPUS:10744229758

SN - 1553-8389

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JO - Cardiovascular Revascularization Medicine

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ER -

Systemic targeted delivery of antisense with perflourobutane gas microbubble carrier reduced neointimal formation in the porcine coronary restenosis model

Abstract

Keywords

ASJC Scopus subject areas

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