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
{"title":"在猪冠状动脉再狭窄模型中，全氟鲁烷气体微泡载体系统靶向递送反义可减少新内膜的形成","authors":"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","DOIUrl":null,"url":null,"abstract":"<div><h3>Hypothesis</h3><p>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-<em>myc</em> in vascular tissue and restenosis after stent implantation.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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-<em>myc</em>. 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 mm<sup>2</sup>, respectively, <em>P</em><.05).</p></div><div><h3>Conclusion</h3><p>In the porcine coronary stent model, systemic targeted delivery of AVI-4126 using PGMC carrier significantly inhibited neointimal formation.</p></div>","PeriodicalId":80261,"journal":{"name":"Cardiovascular radiation medicine","volume":"4 3","pages":"Pages 152-159"},"PeriodicalIF":0.0000,"publicationDate":"2003-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1522-1865(03)00184-7","citationCount":"20","resultStr":"{\"title\":\"Systemic targeted delivery of antisense with perflourobutane gas microbubble carrier reduced neointimal formation in the porcine coronary restenosis model\",\"authors\":\"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\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Hypothesis</h3><p>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-<em>myc</em> in vascular tissue and restenosis after stent implantation.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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-<em>myc</em>. 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 mm<sup>2</sup>, respectively, <em>P</em><.05).</p></div><div><h3>Conclusion</h3><p>In the porcine coronary stent model, systemic targeted delivery of AVI-4126 using PGMC carrier significantly inhibited neointimal formation.</p></div>\",\"PeriodicalId\":80261,\"journal\":{\"name\":\"Cardiovascular radiation medicine\",\"volume\":\"4 3\",\"pages\":\"Pages 152-159\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2003-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/S1522-1865(03)00184-7\",\"citationCount\":\"20\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cardiovascular radiation medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1522186503001847\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cardiovascular radiation medicine","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1522186503001847","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Systemic targeted delivery of antisense with perflourobutane gas microbubble carrier reduced neointimal formation in the porcine coronary restenosis model
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.
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