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CardioVascular and Interventional Radiology

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01-06-2013 | Laboratory Investigation

Balloon Coating with Rapamycin Using an On-site Coating Device

Authors: Jörg Schmehl, Jürgen von der Ruhr, Markus Dobratz, Rainer Kehlbach, Isabelle Braun, Tim-Oliver Greiner, Claus D. Claussen, Boris Behnisch

Published in: CardioVascular and Interventional Radiology | Issue 3/2013

Abstract

Purpose

The efficacy of drug-eluting balloons has been demonstrated in clinical trials. The drug predominantly used is paclitaxel because of its lipophilic properties and the rapid onset of action. The aim of the investigation was to evaluate the feasibility and efficacy of an alternative balloon coating with rapamycin that can be applied on site.

Methods

The balloon coating (3.0/18 and 3.0/12 mm, Cathy No. 4, Translumina GmbH) with rapamycin was conducted with a coating machine (Translumina GmbH). Concentrations were 2, 2 × 2, 3, and 4 %. Measurements regarding the amount of substance released to the vessel wall were carried out on explanted porcine coronaries by means of ultraviolet and visible-light spectroscopy. Inflation time varied between 30 and 120 s. The biological effect of the coating was evaluated in a porcine peripheral overstretch and stent implantation model.

Results

The amount of rapamycin on the balloon surface ranged from 558 ± 108 μg for the 2 % solution to 1,441 ± 228 μg in the 4 % solution. An amount of 95 ± 63–193 ± 113 μg was released into the vessel wall. The quantitative measurements of the angiographic examinations 4 weeks after treatment revealed a reduction of diameter stenosis from 20.6 ± 17.4 % in the control group to 11.6 ± 5.5 % in the drug-eluting balloon group.

Conclusion

A balloon coating with rapamycin omitting an excipient is possible with a dose-adjustable coating machine. However, the biological effects are moderate, which make further optimization of the coating process and evaluation of appropriate excipients necessary.

Werner M, Schmidt A, Freyer M et al (2012) Sirolimus-eluting stents for the treatment of infrapopliteal arteries in chronic limb ischemia: long-term clinical and angiographic follow-up. J Endovasc Ther 19:12–19PubMedCrossRef

Mehilli J, Byrne RA, Wieczorek A, Intracoronary stenting, angiographic restenosis investigators et al (2008) Test efficacy of rapamycin-eluting stents with different polymer coating strategies (ISAR-TEST-3). Randomized trial of three rapamycin-eluting stents with different coating strategies for the reduction of coronary restenosis. Eur Heart J 29:1975–1982PubMedCrossRef

de Waha A, Cassese S, Park DW et al (2012) Everolimus-eluting versus sirolimus-eluting stents: an updated meta-analysis of randomized trials. Clin Res Cardiol 101:461–467PubMedCrossRef

Dake MD, Ansel GM, Jaff MR, Zilver PTX investigators et al (2011) Paclitaxel-eluting stents show superiority to balloon angioplasty and bare metal stents in femoropopliteal disease: 12-month Zilver PTX randomized study results. Circ Cardiovasc Interv 4:495–504PubMedCrossRef

Werk M, Langner S, Reinkensmeier B et al (2008) Inhibition of restenosis in femoropopliteal arteries: paclitaxel-coated versus uncoated balloon: femoral paclitaxel randomized pilot trial. Circulation 118:1358–1365PubMedCrossRef

Tepe G, Zeller T, Albrecht T et al (2008) Local delivery of paclitaxel to inhibit restenosis during angioplasty of the leg. N Engl J Med 358:689–699PubMedCrossRef

Zeller T, Schmitmeier S, Tepe G et al (2011) Drug-coated balloons in the lower limb. J Cardiovasc Surg (Torino) 52:235–243

Finn AV, John M, Nakazawa G et al (2009) Differential healing after sirolimus, paclitaxel, and bare metal stent placement in combination with peroxisome proliferator-activator receptor gamma agonists: requirement for mTOR/Akt2 in PPARgamma activation. Circ Res 105:1003–1012PubMedCrossRef

Radke PW, Joner M, Joost A et al (2011) Vascular effects of paclitaxel following drug-eluting balloon angioplasty in a porcine coronary model: the importance of excipients. EuroIntervention 30(7):730–737CrossRef

10.

Liuzzo JP, Ambrose JA, Coppola JT (2005) Sirolimus- and taxol-eluting stents differ towards intimal hyperplasia and re-endothelialization. J Invasive Cardiol 17:497–502PubMed

11.

Silber S (2005) Cypher versus taxus: are there differences? J Interv Cardiol 18:441–446PubMedCrossRef

12.

Gallo R, Padurean A, Jayaraman T et al (1999) Inhibition of intimal thickening after balloon angioplasty in porcine coronary arteries by targeting regulators of the cell cycle. Circulation 99:2164–2170PubMedCrossRef

13.

De Labriolle A, Pakala R, Bonello L et al (2009) Paclitaxel-eluting balloon: from bench to bed. Catheter Cardiovasc Interv 73:643–652PubMedCrossRef

14.

Scheller B, Hehrlein C, Bocksch W et al (2006) Treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter. N Engl J Med 355:2113–2124PubMedCrossRef

15.

Joner M, Byrne RA, Lapointe JM et al (2011) Comparative assessment of drug-eluting balloons in an advanced porcine model of coronary restenosis. Thromb Haemost 105:864–872PubMedCrossRef

16.

Kelsch B, Scheller B, Biedermann M et al (2011) Dose response to paclitaxel-coated balloon catheters in the porcine coronary overstretch and stent implantation model. Investig Radiol 46:255–263CrossRef

17.

Cremers B, Biedermann M, Mahnkopf D et al (2009) Comparison of two different paclitaxel-coated balloon catheters in the porcine coronary restenosis model. Clin Res Cardiol 98:325–330PubMedCrossRef

18.

Pósa A, Nyolczas N, Hemetsberger R et al (2010) Optimization of drug-eluting balloon use for safety and efficacy: evaluation of the 2nd generation paclitaxel-eluting DIOR-balloon in porcine coronary arteries. Catheter Cardiovasc Interv 76:395–403PubMedCrossRef

19.

Scheller B, Speck U, Abramjuk C et al (2004) Paclitaxel balloon coating, a novel method for prevention and therapy of restenosis. Circulation 110:810–814PubMedCrossRef

20.

Speck U, Scheller B, Abramjuk C et al (2006) Neointima inhibition: comparison of effectiveness of non-stent-based local drug delivery and a drug-eluting stent in porcine coronary arteries. Radiology 240:411–418PubMedCrossRef

21.

Wessely R, Hausleiter J, Michaelis C et al (2005) Inhibition of neointima formation by a novel drug-eluting stent system that allows for dose-adjustable, multiple, and on-site stent coating. Arterioscler Thromb Vasc Biol 25:748–753PubMedCrossRef

22.

Hausleiter J, Kastrati A, Wessely R et al (2005) Investigators of the individualizable durg-eluting stent system to abrogate restenosis project. Prevention of restenosis by a novel drug-eluting stent system with a dose-adjustable, polymer-free, on-site stent coating. Eur Heart J 26:1475–1481PubMedCrossRef

23.

Silber S (2003) Paclitaxel-eluting stents: are they all equal? An analysis of six andomized controlled trials in de novo lesions of 3, 319 patients. J Interv Cardiol 16:485–490PubMedCrossRef

24.

Waksman R, Pakala R (2009) Drug-eluting balloon: the comeback kid? Circ Cardiovasc Interv 2:352–358PubMedCrossRef

25.

van der Giessen WJ, Sorop O, Serruys PW et al (2009) Lowering the dose of sirolimus, released from a nonpolymeric hydroxyapatite coated coronary stent, reduces signs of delayed healing. JACC Cardiovasc Interv 2:284–290PubMedCrossRef

26.

Albrecht T, Speck U, Baier C et al (2007) Reduction of stenosis due to intimal hyperplasia after stent supported angioplasty of peripheral arteries by local administration of paclitaxel in swine. Investig Radiol 42:579–585CrossRef

27.

Cremers B, Milewski K, Clever YP et al (2012) Long-term effects on vascular healing of bare metal stents delivered via paclitaxel-coated balloons in the porcine model of restenosis. Catheter Cardiovasc Interv 80:603–610PubMedCrossRef

28.

Granada JF, Milewski K, Zhao H et al (2011) Vascular response to zotarolimus-coated balloons in injured superficial femoral arteries of the familial hypercholesterolemic Swine. Circ Cardiovasc Interv 4:447–455PubMedCrossRef

Title: Balloon Coating with Rapamycin Using an On-site Coating Device
Authors: Jörg Schmehl
Jürgen von der Ruhr
Markus Dobratz
Rainer Kehlbach
Isabelle Braun
Tim-Oliver Greiner
Claus D. Claussen
Boris Behnisch
Publication date: 01-06-2013
Publisher: Springer-Verlag
Published in: CardioVascular and Interventional Radiology / Issue 3/2013
Print ISSN: 0174-1551
Electronic ISSN: 1432-086X
DOI: https://doi.org/10.1007/s00270-013-0583-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Balloon Coating with Rapamycin Using an On-site Coating Device

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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