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Science to Practice |
Department of Radiology, Duke University Medical Center, Rm 1502, Box 3808, Durham, NC 27710. smith146@mc.duke.edu
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Local delivery of medications to transluminal angioplasty sites to prevent restenosis is receiving worldwide attention. In this issue of Radiology, Schürmann et al (1) describe the biologic response to commercially available stents coated with poly(hydroxymethyl-p-xylylene-co-p-xylylene) (PHPX) and discuss whether this coating may act as a medium for site-specific arterial drug delivery.
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Metallic foils, two self-expandable stents, and one balloon-expandable stent were coated with PHPX and were subjected to in vitro testing with human blood samples to determine thrombogenicity on the basis of platelet adhesion and fibrinogen adsorption. PHPX-coated stents were also placed in normal and abnormal sheep arteries for in vivo determination of compatibility on the basis of acute thrombogenicity and in-stent stenosis. Follow-up after implantation consisted of angiography and intravascular ultrasonography followed by necropsy, with gross and microscopic evaluation of the stents for the degree of intimal hyperplasia. The authors found the coated stents to be at least as thrombogenic as the uncoated stents and more so in several scenarios. The coating alone certainly demonstrated no advantages and some disadvantages regarding patency. However, as the authors note, their study was the basis for the use of the coating as a carrier for drug delivery, and they concluded that additional studies are warranted to evaluate the bonding of drugs to and the release of drugs from the PHPX coating.
The Practice
Clinical use.—In simple terms, there are three basic components to the drug-eluting stent: the stent (stent platform), the carrier agent, and the drug. It is interesting that much of the work being performed today and in the article by Schürmann et al is based on commercially available stent platforms with design characteristics that are aimed at production of a buttressing, rather than a medication-delivery, device. However, the stent does combine attractive mechanical features, such as creation of a smooth postangioplasty surface and elimination of elastic recoil, with simultaneous provision of a means to deliver medication directly to the angioplasty site. Attempts have been made to apply medications onto the bare metallic stent surface, but these efforts have, for the most part, been unsuccessful (2). The current focus is, therefore, directed to carrier agents that bind to both the metal stent and the medication.
A number of factors should be present for the carrier to be effective (2). Ideally, the carrier should be biologically inert, especially as regards thrombosis and inflammation. It should possess predicable drug-eluting kinetics and a high-quality surface integrity and should not alter the stent platform or react with the drug. The carrier should incorporate attractive logistic features, including stability with a reasonable shelf life and, of course, low cost. The PHPX coating described by Schürmann et al appears to have some of these features. In particular, it does not alter the stent, is homogeneous, and has high mechanical stability. It is, unfortunately, relatively thrombogenic; the other factors have not yet been tested. To date, however, no carrier is completely inert. van der Giessen et al (3) implanted stents loaded with eight different polymer coatings into porcine coronary arteries and found a marked inflammatory reaction in all.
Drug-eluting stents are now a reality in interventional practices in the United States. On April 24, 2003, one manufacturer received U.S. Food and Drug Administration approval to market the first antimitotic drug-eluting stent (CYPHER Sirolimus-eluting Coronary Stent; Cordis, Miami, Fla). This stent consists of an already widely used balloon-expandable coronary stent (Bx Velocity; Cordis) coated with a blend of two polymers, polyethylene-co-vinyl acetate (PEVA) and poly N-butyl methacrylate (PBMA). Food and Drug Administration approval of this stent was based on very positive clinical results, and the stent is already having an enormous impact on medical practice, leading some to even question the future of coronary artery bypass grafting (4).
Future opportunities and challenges.—There is a mounting rush to develop better platforms that are specialized for drug delivery, to synthesize improved carriers with characteristics that facilitate precise drug delivery, and to discover superior drugs to battle the problem of arterial restenosis. The work of Schürmann et al (1) demonstrates such ongoing intense research efforts, specifically in the area of carriers. If the early results are predictive and research efforts hold pace, drug-eluting stents will be a major breakthrough in the battle against restenosis after transluminal angioplasty.
Summary
The authors have verified the in vitro and in vivo stability of a polymer coating on commercially available stents. The next phase will be to establish whether these polymer-coated stents can serve as an effective medium for drug-elution.
FOOTNOTES
See also the article by Schürmann et al in this issue.
REFERENCES
This article has been cited by other articles:
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  L. Tang, X. Chen, S. Tang, T. LaLonde, and J. M Gardin Granulation encapsulated stent: a new therapeutic approach for vascular implantation Heart, February 1, 2007; 93(2): 238 - 243. [Abstract] [Full Text] [PDF]
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