Local Drug Delivery via a Coronary Stent With Programmable Release Pharmacokinetics

Finkelstein, Ariel; McClean, Dougal; Kar, Saibal; Takizawa, Kazuyasu; Varghese, Kiron; Baek, Namjin; Park, Kinam; Fishbein, Michael C.; Makkar, Raj; Litvack, Frank; Eigler, Neal

doi:10.1161/01.cir.0000050367.65079.71

Cited by 160 publications

(97 citation statements)

References 18 publications

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“…Pigs were evaluated 4 weeks after stenting because neointimal formation peaks at that time in this particular animal model, 22 and studies evaluating stent-based drug delivery in porcine coronaries were performed at identical time points. 20,23,24 Despite these limitations, given the significant reduction of neointima formation by rapamycin-eluting microporous stents compared with bare-metal stents, it is suggested that this novel drug-eluting stent concept is effective. The concept of the ISAR coating system constitutes a unique approach for the creation of efficient DES, enabling cardiologists to choose one or several drugs in the desired concentration within a percutaneous coronary interventional procedure at their discretion.…”

Section: Study Limitations and Conclusionmentioning

confidence: 99%

Inhibition of Neointima Formation by a Novel Drug-Eluting Stent System That Allows for Dose-Adjustable, Multiple, and On-Site Stent Coating

Wessely¹,

Hausleiter²,

Michaelis³

et al. 2005

ATVB

124

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Objective-The risk of in-stent restenosis can be considerably reduced by stents eluting cytostatic compounds. We created a novel drug-eluting stent system that includes several new features in the rapidly evolving field of stent-based drug delivery. Methods and Results-The aim of the present study was the preclinical evaluation of a stent-coating system permitting individual, on-site coating of stents with a unique microporous surface allowing for individualizable, dose-adjustable, and multiple coatings with identical or various compounds, designated ISAR (individualizable drug-eluting stent system to abrogate restenosis). Stents were coated with 0.75% rapamycin solution, and high-performance liquid chromatography (HPLC)-based determination of drug release profile indicated drug release for Ͼ21 days. Rapamycin-eluting microporous (REMP) stents implanted in porcine coronary arteries were safe. To determine the efficacy of REMP stents, this novel drug-eluting stent platform was compared with the standard sirolimus-eluting stent. At 30 days, in-stent neointima formation in porcine coronary arteries was similar in both groups, yielding a significant decrease of neointimal area and injury-dependent neointimal thickness compared with bare-metal stents. Conclusion-The ISAR drug-eluting stent platform as a novel concept for stent coating allows for a safe, effective, on-site stent coating process, thus justifying further clinical evaluation to decrease in-stent restenosis in humans. Key Words: drug-eluting stent Ⅲ rapamycin Ⅲ sirolimus Ⅲ stent platform I n-stent restenosis, the major adverse outcome after percutaneous coronary stent placement, 1 can be successfully reduced by drug-eluting stents (DES) releasing cytostatic compounds. Numerous large clinical trials consistently revealed an impressive reduction of in-stent restenosis in de novo lesions by DES. 2-4 However, in specific patient subsets, such as insulin-dependent diabetic subjects, 5 or in challenging interventional scenarios, like bifurcation stenting, 6 the rate of restenosis remains to be substantial at this point. Moreover, the outcome of treatment of in-stent restenosis within DES is currently not satisfactorily solved. 7 Dose adjustments at the discretion of the interventional cardiologist to individualize the dosage of the compound on the drug-eluting stent may be desirable to enable an individual dose adjustment for specific lesion or patient subsets, eg, higher rapamycin doses for diabetic patients. Further, in future scenarios, stent-coating with multiple compounds, for instance to inhibit smooth muscle cell proliferation and promote re-endothelialization, may be desirable. In addition, the presently approved drugeluting stent platforms use a polymer-based coating for retardation of drug release. There is evidence that application of polymers may lead to hypersensitivity reactions and, in few cases, late cardiac death. 8 Furthermore, the issue of late-stent thrombosis in DES, particularly after discontinuation of antiplatelet therapy, is currently s...

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Section: Study Limitations and Conclusionmentioning

confidence: 99%

Inhibition of Neointima Formation by a Novel Drug-Eluting Stent System That Allows for Dose-Adjustable, Multiple, and On-Site Stent Coating

Wessely¹,

Hausleiter²,

Michaelis³

et al. 2005

ATVB

124

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“…Thus, drug release from these systems can be achieved by: (1) diffusion of drug from the polymeric matrix, (2) dissolution of drug into the release medium; and (3) biodegradation of polymeric chains. By careful optimization of the drug-polymer ratio (Kamath et al, 2006), drug density (Alexis et al, 2004), drugpolymer selection (Finkelstein et al, 2003), physical dimensions of the coated film and process parameters, adequate control over elution rate can be achieved. During our studies (Raval et al, 2007) on controlled elution of paclitaxel using a blend of biodegradable polymers from the class of polylactides and co-polymers of polylactide-coglycolide, it was observed that adequate control over drug release could be attained by coating the stent in multiple layers.…”

Section: Mechanisms Of Drug Release Kinetics For Coronary Stentsmentioning

confidence: 99%

“…The findings have triggered the design and evolution of the next generation of coatings and novel coating strategies. Conor Medsytems has developed a cobaltchromium stent whose struts are laser drilled and the small holes function as reservoirs that can be filled with drug-polymeric blends to attain programmable drug elution kinetics to cope with restenosis ( Figure 2) (Finkelstein et al, 2003). This system allows controlling the direction (luminal, mural, both) of paclitaxel elution by a fully erodible PLGA polymer.…”

Section: Various Approaches For Drug Delivery From Stentsmentioning

confidence: 99%

Mechanism of controlled release kinetics from medical devices

Raval

Parikh

2010

Braz. J. Chem. Eng.

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-Utilization of biodegradable polymers for controlled drug delivery has gained immense attention in the pharmaceutical and medical device industry to administer various drugs, proteins and other biomolecules both systematically and locally to cure several diseases. The efficacy and toxicity of this local therapeutics depends upon drug release kinetics, which will further decide drug deposition, distribution, and retention at the target site. Drug Eluting Stent (DES) presently possesses clinical importance as an alternative to Coronary Artery Bypass Grafting due to the ease of the procedure and comparable safety and efficacy. Many models have been developed to describe the drug delivery from polymeric carriers based on the different mechanisms which control the release phenomenon from DES. Advanced characterization techniques facilitate an understanding of the complexities behind design and related drug release behavior of drug eluting stents, which aids in the development of improved future drug eluting systems. This review discusses different drug release mechanisms, engineering principles, mathematical models and current trends that are proposed for drug-polymer coated medical devices such as cardiovascular stents and different analytical methods currently utilized to probe diverse characteristics of drug eluting devices.

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“…Research has already shown that drugs can be encapsulated in nanospheres 6 or erodible self-assembled structures 7 or conjugated to well-defined multivalent macromolecules such as dendrimers (highly branched polymers). 8 These mechanisms can improve bioavailability and enable continued release, thereby controlling the initial dose, improving effectiveness, and widening the therapeutic window.…”

Section: Drug Delivery and Therapeuticsmentioning

confidence: 99%

Recommendations of the National Heart, Lung, and Blood Institute Nanotechnology Working Group

et al. 2003

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Abstract-Recent rapid advances in nanotechnology and nanoscience offer a wealth of new opportunities for diagnosis and therapy of cardiovascular, pulmonary, and hematologic diseases and sleep disorders. To review the challenges and opportunities offered by these nascent fields, the National Heart, Lung, and Blood Institute convened a Working Group on Nanotechnology. Working Group participants discussed the various aspects of nanotechnology and its applications to heart, lung, blood, and sleep (HLBS) diseases. This report summarizes their discussions according to scientific opportunities, perceived needs and barriers, specific disease examples, and recommendations on facilitating research in the field. Key Words: nanotechnology Ⅲ cardiovascular diseases Ⅲ lung Ⅲ blood diseases Ⅲ sleep T he burgeoning new field of nanotechnology, opened up by rapid advances in science and technology, creates myriad new opportunities for advancing medical science and disease treatment. In the near future, nanotechnology will play an increasingly significant role in the everyday practice of cardiologists, pulmonologists, and hematologists. Nanotechnology and nanoscience focus on materials at the atomic, molecular, and supramolecular level, aiming to control and manipulate these new materials by precisely configuring atoms and molecules, producing novel molecular assemblies and designing systems of self-assembly to create supramolecular devices on the scale of an individual cell and smaller.In his prescient address to the American Physical Society in 1959, Richard Feynman foresaw that "at the atomic level, we have new kinds of forces and new kinds of possibilities, new kinds of effects. The problems of manufacture and reproduction of materials will be quite different." Because the behavior of materials, structures, and devices at the nanoscale (in the range of 1 to 100 nm) differs from the macroscopic world, nanostructures display unique mechanical, electrical, chemical, and optical properties. Understanding and controlling such properties is challenging, but harnessing them will provide exciting new opportunities for research, diagnosis, and therapy of heart, lung, blood, and sleep (HLBS) disorders. The nanoscale is prevalent in natural systems, because many important functional components of living cells fit within this size classification, but few nanoscale drugs or diagnostic, therapeutic, or repair devices have been developed. Nanoscale properties allow high densities of function in small packages to minimize invasiveness and facilitate "smarter" therapeutic interventions with increased specificity of delivery and action, decreased side effects, and the capability to respond to external stimuli and report to external receivers.The National Heart, Lung, and Blood Institute (NHLBI) wishes to foster the application of nanotechnology to HLBS research and disorders. A Request for Information (RFI) was developed, with advice from scientists and physicians with interests in nanotechnology, to canvas the broader scientific community on ...

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Local Drug Delivery via a Coronary Stent With Programmable Release Pharmacokinetics

Cited by 160 publications

References 18 publications

Inhibition of Neointima Formation by a Novel Drug-Eluting Stent System That Allows for Dose-Adjustable, Multiple, and On-Site Stent Coating

Inhibition of Neointima Formation by a Novel Drug-Eluting Stent System That Allows for Dose-Adjustable, Multiple, and On-Site Stent Coating

Mechanism of controlled release kinetics from medical devices

Recommendations of the National Heart, Lung, and Blood Institute Nanotechnology Working Group

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