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Phosphorylcholine is a zwitterionic phospholipid found on the outer surface of red blood cell membranes [1] . In the field of Interventional Cardiology, Phosphorylcholine is used as a synthetic polymer based coating, applied to drug-eluting stents, to prevent the occurrence of coronary artery restenosis. The first application of this approach for use on stents evolved from efforts by Hayward and Chapman et al., who demonstrated that the Phosphorylcholine component of the outer surface of the erythrocyte bilayer was non-thrombogenic [2] . To date, more than 120,000 Phosphorylcholine-coated stents have been implanted in patients with no apparent deleterious effect in the long term compared to bare metal stent technologies.[3]

Contents

Phosphorylcholine Polymer based Drug-Eluting Stents

Drug-Eluting Stents are used by Interventional Cardiologists, operating on patients with Coronary Artery Disease. The Stent is inserted into the artery via a balloon angioplasty. This will dialate the diameter of the coronary artery and keep it fixed in this phase so that more blood flows through the artery without the risk of blood clots (Atherosclerosis)[4]. Phosphorylcholine is used as the polymer based coating of Drug-Eluting Stents because its molecular design improves surface biocompatibility and lowers the risk of causing inflammation or thrombosis. Polymer coatings of the stents that deliver the anti-proliferative drug, Zotarolimus, to the arterial vessel wall are key components of these revolutionary medical devices. For targeted local delivery of Zotarolimus to the artery, the drug is incorporated into a methacrylate-based copolymer that includes a synthetic form of Phosphorylcholine. This use of biomimicry, or the practice of using polymers that occur naturally in biology, provides a coating, with minimal thrombus deposition and no adverse clinical effect on late healing of the arterial vessel wall. Not only is the coating non-thrombogenic, but it also exhibits other features that should be present when applying such a material to a medical device for long-term implantation. These include durability, neutrality to the chemistry of the incorporated drug and ability for sterilization using standard methods which do not affect drug structure or efficacy.

The ZoMaxx Zotarolimus-Eluting Stent

The third Zotarolimus-eluting coronary stent to reach clinical trials is the ZoMaxx stent. Developed by Abbott Vascular, the ZoMaxx stent was designed for thin strut width, low profile, and high radial strength, while still maintaining adequate visibility on fluoroscopy. [5] The ZoMaxx stent delivers its antiproliferative agent through a series of Phosphorylcholine polymer coats, so that the completed stent displays experimental elution kinetics qualitatively similar to the Cypher stent.[6] A series of in vitro and in vivo studies were conducted to establish an elution profile, which would deliver drug over a time frame consistent with events associated with the restenotic process. It was determined that drug elution could be controlled by placement of a Phosphorylcholine topcoat over a Phosphorylcholine/drug layer, and that the elution kinetics were dependent on the thickness of this top layer.[7] Results of these studies indicated that the most rapid drug elution occurred when no topcoat was present, and that elution was slowed in a graded fashion when topcoats of increasing thickness were applied. Therefore, during the first week after implant, a Phosphorylcholine topcoat of 5 μg/mm of stent length resulted in a drug release of approximately 60% during the first week after implant, followed by an additional 20% during the second week. The remaining 20% is released over the next 2 weeks, so that virtually all the drug has been eluted over a 1-month period..[6]

See also

Notes and references

  1. ^ S. Chen, J. Zheng, L. Li and S. Jiang, Strong resistance of phosphorylcholine self-assembled monolayers to protein adsorption: insights into nonfouling properties of zwitterionic materials, J. Am. Chem. Soc. 127 (2005), pp. 14473–14478. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (62)[11]. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T3R-4JDN677-8&_user=128860&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000010638&_version=1&_urlVersion=0&_userid=128860&md5=4f6c66e34975a875c63d472a8895cd66 Retrieved on 2009-02-09
  2. ^ J.A. Hayward and D. Chapman, Biomembrane surfaces as models for polymer design: the potential for haemocompatibility, Biomaterials 5 (1984), pp. 135–142. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T3R-4JDN677-8&_user=128860&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000010638&_version=1&_urlVersion=0&_userid=128860&md5=4f6c66e34975a875c63d472a8895cd66 Retrieved on 2009-02-09
  3. ^ A.L. Lewis, L.A. Tolhurst and P.W. Stratford, Analysis of a phosphorylcholine-based polymer coating on a coronary stent pre- and post-implantation, Biomaterials 23 (2002), pp. 1697–1706.http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T3R-4JDN677-8&_user=128860&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000010638&_version=1&_urlVersion=0&_userid=128860&md5=4f6c66e34975a875c63d472a8895cd66 Retrieved on 2009-02-09
  4. ^ A. L. Lewis, P. W. Stratford, A. L. Lewis, R. T. Freeman, L. Hughes, R. P. Redman, L. A. Tolhurst and T. A. Vick, Abstracts of UKSB 1st Annual Conference, July 2000. http://www.springerlink.com/content/m71v821028035485/ Retrieved on 2009-02-09
  5. ^ S. Shrivastava, A novel trilayered metal composite stent, Am. J. Cardiol. 94 (2004), p. 158E.http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T3R-4JDN677-8&_user=128860&_coverDate=06%2F03%2F2006&_rdoc=1&_fmt=full&_orig=search&_cdi=4953&_sort=d&_docanchor=&view=c&_acct=C000010638&_version=1&_urlVersion=0&_userid=128860&md5=2a42c69f1da50de47eac8b2cd44ed1c6#bib48 Retrieved on 2009-02-09
  6. ^ a b M. DuVall, Q. Ji, A. Clifford, C.M. Barry, S.A. Nowak, K.M. Sabaj, D.A. Zielinski, G. Smits, J. Zhang, K. Cromack, H. Dube, L.B. Schwartz and R.W. Krasula, ABT-578 elution profile and arterial penetration using the ZoMaxx drug-eluting stent (abstract), Am. J. Cardiol. 94 (2004), p. 223E. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T3R-4JDN677-8&_user=128860&_coverDate=06%2F03%2F2006&_rdoc=1&_fmt=full&_orig=search&_cdi=4953&_sort=d&_docanchor=&view=c&_acct=C000010638&_version=1&_urlVersion=0&_userid=128860&md5=2a42c69f1da50de47eac8b2cd44ed1c6#bib56 Retrieved on 2009-02-09
  7. ^ S.A. Nowak, K. Sabaj, D. Zielinski, M. DuVall, A. Clifford, C. Barry, G. Smits, K. Cromack, H. Dube, L. Schwartz and R. Krasula, The effect of adding a polymer topcoat on the elution rate from drug-eluting stents, CRT, Abstract 503 (2005).http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T3R-4JDN677-8&_user=128860&_coverDate=06%2F03%2F2006&_rdoc=1&_fmt=full&_orig=search&_cdi=4953&_sort=d&_docanchor=&view=c&_acct=C000010638&_version=1&_urlVersion=0&_userid=128860&md5=2a42c69f1da50de47eac8b2cd44ed1c6#bib57 Retrieved on 2009-02-09

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