The future of drug-eluting stents

Kukreja, Neville; Onuma, Yoshinobu; Daemen, Joost; Serruys, Patrick W.

doi:10.1016/j.phrs.2008.01.012

Cited by 103 publications

(90 citation statements)

References 83 publications

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“…Considering recent developments in DES design (33) and longer-term clinical safety reports (34,35), we envision that the nanoburrs may be useful for a subset of patients who are currently unable to receive DESs. This group may have preexisting comorbidities, planned surgeries, or lesions not amenable for stenting (longer lesions, branch points, and diffusely diseased, smaller arteries) (2).…”

Section: Discussionmentioning

confidence: 99%

“…Whereas Taxol, an FDA-approved formulation for systemic paclitaxel delivery, has been associated with various side effects that narrow its therapeutic window (26), the nanoburrs were shown to have a ≥3.5-fold improved maximum tolerated dose over Taxol in safety studies. Also, their prolonged circulatory half-life may enhance retention at sites where permeability is enhanced (33). Furthermore, the ability to surface functionalize NPs means that not only peptides, but other types of targeting ligands such as antibodies and small molecules may be added to improve drug delivery to sites of vascular injury.…”

Section: Discussionmentioning

confidence: 99%

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In vivo prevention of arterial restenosis with paclitaxel-encapsulated targeted lipid–polymeric nanoparticles

Chan

Rhee

Drum

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

130

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Following recent successes with percutaneous coronary intervention (PCI) for treating coronary artery disease (CAD), many challenges remain. In particular, mechanical injury from the procedure results in extensive endothelial denudation, exposing the underlying collagen IV-rich basal lamina, which promotes both intravascular thrombosis and smooth muscle proliferation. Previously, we reported the engineering of collagen IV-targeting nanoparticles (NPs) and demonstrated their preferential localization to sites of arterial injury. Here, we develop a systemically administered, targeted NP system to deliver an antiproliferative agent to injured vasculature. Approximately 60-nm lipid-polymeric NPs were surface functionalized with collagen IV-targeting peptides and loaded with paclitaxel. In safety studies, the targeted NPs showed no signs of toxicity and a ≥3.5-fold improved maximum tolerated dose versus paclitaxel. In efficacy studies using a rat carotid injury model, paclitaxel (0.3 mg/kg or 1 mg/kg) was i.v. administered postprocedure on days 0 and 5. The targeted NP group resulted in lower neointima-to-media (N/M) scores at 2 wk versus control groups of saline, paclitaxel, or nontargeted NPs. Compared with sham-injury groups, an ∼50% reduction in arterial stenosis was observed with targeted NP treatment. The combination of improved tolerability, sustained release, and vascular targeting could potentially provide a safe and efficacious option in the management of CAD. P ercutaneous coronary interventions (PCIs) using drug-eluting stents (DESs) are credited with significant reductions in vessel restenosis, due to the effective combination of a drug delivery system and mechanical scaffold (1). Despite the extensive clinical use of DESs to maintain vascular patency, not all coronary lesions are amenable to DES placement (2). In addition, DESs are associated with delayed endothelialization (3) and increased thrombogenicity (4, 5) that require extended antiplatelet treatment (6). In some cases, only bare metal stents (BMSs) may be applied, which lack the benefit of antirestenotic therapy and instead stimulate neointimal smooth muscle cell (SMC) proliferation (7,8).Nanomedicines may offer improvements to existing clinical treatments, including those for cardiovascular disorders (9, 10). Sub-100-nm organic nanoparticles (NPs) combine useful features of ultrasmall size (11, 12), surface modification (13), controlled drug release, biodegradability, and biocompatibility (14). Liposomal, polymeric, and albumin-based NPs have been formulated to improve drug solubility and deliver paclitaxel at doses higher than otherwise possible in circulation (15-17). Temporal control of drug delivery may facilitate endothelial healing after injury, as NPs may be used to deliver antiproliferative agents to the vascular wall when neointimal proliferation is most active, followed by complete degradation and clearance (18). Targeted NPs that bind to exposed antigens in injured arteries may help to achieve therapeutic doses at sites of injury, b...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

In vivo prevention of arterial restenosis with paclitaxel-encapsulated targeted lipid–polymeric nanoparticles

Chan

Rhee

Drum

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

130

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“…The drugs inhibit the neointimal growth and ECM reproduction. Therefore, the current strategies of optimizing DES focus on preparing new platforms, new coatings and new techniques of elution [34]. Up to date, different designs of new platforms (e.g.…”

Section: Drug Eluting Stentsmentioning

confidence: 99%

Current status of research and application in vascular stents

Yang

Maitz

2013

Chin. Sci. Bull.

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Cardiovascular diseases have been the leading cause of death in modern society. Using vascular stents to treat these coronary and peripheral artery diseases has been one of the most effective and rapidly adopted medical interventions. During the twenty-five years' development of vascular stents, revolutionary cardiovascular stents like drug eluting stents and endothelial progenitor cells capture stents have emerged. In this review, the evolution of vascular stents is summarized, aiming to provide a glimpse into the future of vascular stents. Advanced designs, focusing on the investigations of new substrates, new platforms, new drugs and new biomolecules are currently under evaluation with promising clinical studies. The concept of "time sequence functional stent" has been raised in this paper. It presents anti-proliferative properties in the first phase after implantation and subsequently support endothelialization. It also shows long-term inertness without release of toxic ions or toxic degradation products. The success of this concept is briefly presented with a clinical study in this model stents.

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“…The SES design consists of a stainless steel platform coated with a permanent polymer containing sirolimus 140 μg/cm 2 , 80% of which is released within 30 d. The PES design is also composed of a stainless steel platform with a permanent polymer coating combined with 1 μg/mm 2 paclitaxel; 10% of the paclitaxel is released within 2 wk after stent deployment, although 90% of it remains in the polymer forever [24,26] . The presence of permanent polymers in the vessel arterial wall adds an additional factor that influences local responses and may alter processes involved in neointimal formation.…”

Section: First Des Designsmentioning

confidence: 99%

Advantages and disadvantages of biodegradable platforms in drug eluting stents

Rodriguez-Granillo

Rubilar²,

Rodríguez-Granillo³

et al. 2011

WJC

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Coronary angioplasty with drug-eluting stent (DES) implantation is currently the most common stent procedure worldwide. Since the introduction of DES, coronary restenosis as well as the incidence of target vessel and target lesion revascularization have been significantly reduced. However, the incidence of very late stent thrombosis beyond the first year after stent deployment has more commonly been linked to DES than to baremetal stent (BMS) implantation. Several factors have been associated with very late stent thrombosis after DES implantation, such as delayed healing, inflammation, stent mal-apposition and endothelial dysfunction. Some of these adverse events were associated with the presence of durable polymers, which were essential to allow the elution of the immunosuppressive drug in the first DES designs. The introduction of erodable polymers in DES technology has provided the potential to complete the degradation of the polymer simultaneously or immediately after the release of the immunosuppressive drug, after which a BMS remains in place.Several DES designs with biodegradable (BIO) polymers have been introduced in preclinical and clinical studies, including randomized trials. In this review, we analyze the clinical results from 6 observational and randomized studies with BIO polymers and discuss advantages and disadvantages of this new technology.

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The future of drug-eluting stents

Cited by 103 publications

References 83 publications

In vivo prevention of arterial restenosis with paclitaxel-encapsulated targeted lipid–polymeric nanoparticles

In vivo prevention of arterial restenosis with paclitaxel-encapsulated targeted lipid–polymeric nanoparticles

Current status of research and application in vascular stents

Advantages and disadvantages of biodegradable platforms in drug eluting stents

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