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HISTORICAL BACKGROUND

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The concept of delivering antiproliferative drugs via balloon angioplasty has been around for several decades. However, the specific idea of developing a drug-coated balloon (DCB) system originated from the seminal work of professor Ulrich Speck in the use of contrast agents as carriers of antiproliferative drugs.1 At the early stages of his research, it was found that paclitaxel solubility was significantly increased when mixed when contrast agents. Experimental data showed that a repeated intracoronary bolus injection of a taxane-iopromide formulation resulted in significant reduction of neointimal proliferation in the porcine model of restenosis.2,3 In 2001, the concept of mixing iopromide with paclitaxel in a form of a balloon coating was reduced to practice and validated at the experimental level.4 This original DCB formulation was then clinically validated in small randomized controlled studies in the coronary in-stent restenosis5 and de novo superficial femoral artery stenosis settings.6,7 Stimulated by these early clinical results, several DCB programs were started following a similar technologic approach of using hydrophilic carriers as a method to transport paclitaxel into the vessel wall after balloon dilatation.

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TECHNOLOGIC APPROACH

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The development of drug-eluting stents (DESs) dramatically reduced the long-term rate of reintervention and improved clinical outcomes among patients undergoing percutaneous coronary interventions.4 However, despite their continuous technologic evolution and well-validated clinical efficacy, long-term complications (eg, target lesion revascularization) continue to occur.8 Several autopsy and in vivo imaging studies suggest delayed healing of the permanently implanted stent as the most important biologic mechanism responsible for these events.9,10 As a result, stent-based drug delivery technologies continue to evolve aiming to minimize the amount of permanent implantable components (ie, polymer) left behind following DES implantation.11

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The concept of developing a balloon-based drug delivery system to prevent arterial restenosis was based on the hypothesis that a durable effect on neointimal proliferation could be achieved following single-drug delivery and potentially minimizing the impact of the chronically implantable components.12 This technologic approach appeared to contradict historical experimental and clinical data suggesting that sustained tissue exposure to therapeutic levels of drug was necessary to effectively inhibit neointimal proliferation.13 Due to its particular delivery mechanism and resulting pharmacokinetic profile, the promising results shown by the early DCB trials were originally challenged under the premise that sustained drug release was needed to attain long-term clinical efficacy.5,6,8

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COATING FEATURES AND MECHANISM OF ACTION

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All DCBs developed to date use paclitaxel due to its high lipophilic profile, potent antiproliferative effect, and chemical stability following tissue delivery.14 Paclitaxel has shown to inhibit cell proliferation and migration due to an irreversible stabilization of intracellular microtubules, resulting in inhibition of cell replication during metaphase and anaphase of mitosis.15 Early experimental data showed that drug carriers are needed to transfer and maintain paclitaxel tissue ...

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