Dose-dependent vascular response following delivery of sirolimus via fast releasing, biodegradable polymer stent matrix: an experimental study in the porcine coronary model of restenosis

Buszman, Piotr P.; Orlik, Bartłomiej; Pajak, Jacek; Jelonek, Michał; Krauze, Agata; Janas, Adam; Legutko, Jacek; Wojakowski, Wojciech; Milewski, Krzysztof

doi:10.5603/kp.a2015.0085

Cited by 4 publications

(5 citation statements)

References 23 publications

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“…Permanent polymers in drug-eluting stents used to overcome restenosis adversely affect the stented vascular restoration and prolong the inflammatory reaction process. Eventually, they contribute to late and very late thrombosis (9,18). When a biodegradable polymer is used, the drug is absorbed from the stent surface after elution, leaving only the neointima-and endothelium-coated metal stent without further irritating the arterial wall.…”

Section: Discussionmentioning

confidence: 99%

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Atlas drug-eluting coronary stents inhibits neointimal hyperplasia in sheep modeling

Dinc

Yerebakan

2023

Preprint

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Background: Coronary artery disease (CAD) is one of the leading causes of mortality and morbidity worldwide. Many patients with CAD require mechanical revascularization. However, restenosis after minimally invasive intervention is a major problem for these patients. Fortunately, due to the controlled drug delivery properties of drug-eluting stents (DES), this problem seems to be significantly overcome. In this study, the pharmacodynamic and pharmacokinetic properties of Atlas Drug-eluting Coronary Stents coated with PLGA were evaluated. Materials and Methods This study was carried out in 20 non-atherosclerotic female sheep, divided into four groups that included 4 study and 1 control randomly assigned to each group. The animals in the study groups were stented with Atlas Drug-eluting Coronary Stents and the pharmacodynamic and pharmacokinetic properties were evaluated. Results: A statistically important effectivity of sirolimus on the vascular endothelium was shown. With time, the decrease in sirolimus in blood samples was statistically significant. In the others, no clinically significant side effects were observed. Conclusions The results in this study showed a significant reduction in neointimal hyperplasia after experimental implantation of Atlas Drug-eluting Coronary Stents coated with PLGA polymer. Pharmacokinetic studies also showed that the stent did not release significant left sirolimus after 28 days.

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Section: Discussionmentioning

confidence: 99%

“…This improves arterial vascular restoration and reduces the inflammatory reaction. It also reduces the need for long-term antiplatelet therapy (18).…”

Section: Discussionmentioning

confidence: 99%

Atlas drug-eluting coronary stents inhibits neointimal hyperplasia in sheep modeling

Dinc

Yerebakan

2023

Preprint

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“…Investigator-driven initiatives are important to advance knowledge of new DES. A previous animal study reported the value of the Alex stent in inhibiting neointimal proliferation [8]. Another study, also from Poland, used optical coherence tomography to assess the mechanistic results of the Alex stent [9].…”

Section: Present Studymentioning

confidence: 98%

Novel sirolimus-eluting stents

Alfonso

Rivero²

2016

Coronary Artery Disease

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Drug-eluting stents (DES) have revolutionized interventional cardiology [1][2][3]. Because of their strong ability to inhibit neointimal proliferation, currently, DES represent the default strategy during coronary interventions [1][2][3]. Initially, first-generation DES proved to be very effective in reducing the restenosis rate and the need for repeated interventions [4]. These early devices included sirolimus-DES (SES) and paclitaxel-DES (PES). The RAVEL trial represented a milestone showing that, in highly selected patient and lesion subsets, a restenosis rate of 0% was indeed possible with DES [4]. This was a dream come true for interventional cardiologists. However, it soon became clear that restenosis still occurred after DES implantation, especially when these devices were used in highly complex clinical and anatomic scenarios [1][2][3]. From the very beginning, SES proved to be more effective than PES in suppressing neointimal growth. In fact, preliminary studies suggesting that the larger late loss observed with PES compared with SES had no relevant clinical implications were soon refuted by subsequent larger studies reporting the clinical benefit associated with the smaller late loss provided by SES [5].However, the risk of stent thrombosis was not reduced by first-generation DES [1][2][3][4][5]. In fact, these devices were associated with a very low, but marginally higher risk of very-late stent thrombosis compared with bare-metal stents. Delayed endothelization, inflammation, fibrin deposition, neoatherosclerosis, allergic or, actually, a real toxic effect on the vessel wall, were considered putative underlying pathologic substrates accounting for this feared complication [3]. The permanent polymers used in these early DES were a cause for concern in this respect.Second-generation DES addressed most of these limitations and eventually moved the field forward [1,2]. These devices proved to be not only more effective but also safer than first-generation DES [1,2]. Major advances in platform designs, with much thinner and more flexible struts and appealing metal alloys (shifting from stainless steel to cobalt-chromium or platinum-chromium), were made. Moreover, permanent polymers evolved to become truly biocompatible. Last but not least, a new family of highly lipophilic limus drugs was developed in an attempt to improve results. In this setting, excellent results were obtained and a renewed feeling of confidence suggested that the duration of dual antiplatelet therapy could be reduced. However, most head-to-head DES studies showing the benefits of second-generation DES selected PES as the comparator [1]. Beating the results of firstgeneration SES was eventually possible, but proved to be more challenging [2].The term 'third-generation' DES generates major controversy [3]. For many investigators most new DES should just be considered sequential iterations of former devices and do not represent clear-cut breakthroughs. However, the advent of fully biodegradable polymers clearly constitutes a qualitative t...

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“…The biodegradable stent is thus considered a promising device for local treatment of ureter diseases. Moreover, the technology of rapamycin-eluting bioresorbable stent has become mature in treating coronary artery narrowing in the past decade [ 38 , 39 ]. In this study, a rapamycin-eluting bioresorbable stent is employed to test the hypothesis of improving ureteral stricture with local release of mTOR inhibitors (mTORi).…”

Section: Introductionmentioning

confidence: 99%

Biodegradable Stent with mTOR Inhibitor-Eluting Reduces Progression of Ureteral Stricture

Su²,

Chang

et al. 2021

IJMS

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In this study, we investigated the effect of mTOR inhibitor (mTORi) drug-eluting biodegradable stent (DE stent), a putative restenosis-inhibiting device for coronary artery, on thermal-injury-related ureteral stricture in rabbits. In vitro evaluation confirmed the dose-dependent effect of mTORi, i.e., rapamycin, on fibrotic markers in ureteral component cell lines. Upper ureteral fibrosis was induced by ureteral thermal injury in open surgery, which was followed by insertion of biodegradable stents, with or without rapamycin drug-eluting. Immunohistochemistry and Western blotting were performed 4 weeks after the operation to determine gross anatomy changes, collagen deposition, expression of epithelial–mesenchymal transition markers, including Smad, α-SMA, and SNAI 1. Ureteral thermal injury resulted in severe ipsilateral hydronephrosis. The levels of type III collagen, Smad, α-SMA, and SNAI 1 were increased 28 days after ureteral thermal injury. Treatment with mTORi-eluting biodegradable stents significantly attenuated thermal injury-induced urinary tract obstruction and reduced the level of fibrosis proteins, i.e., type III collagen. TGF-β and EMT signaling pathway markers, Smad and SNAI 1, were significantly modified in DE stent-treated thermal-injury-related ureteral stricture rabbits. These results suggested that intra-ureteral administration of rapamycin by DE stent provides modification of fibrosis signaling pathway, and inhibiting mTOR may result in fibrotic process change.

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Dose-dependent vascular response following delivery of sirolimus via fast releasing, biodegradable polymer stent matrix: an experimental study in the porcine coronary model of restenosis

Cited by 4 publications

References 23 publications

Atlas drug-eluting coronary stents inhibits neointimal hyperplasia in sheep modeling

Atlas drug-eluting coronary stents inhibits neointimal hyperplasia in sheep modeling

Novel sirolimus-eluting stents

Biodegradable Stent with mTOR Inhibitor-Eluting Reduces Progression of Ureteral Stricture

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