Sustained Efficacy and Arterial Drug Retention by a Fast Drug Eluting Cross-Linked Fatty Acid Coronary Stent Coating
| Autor: | Elazer R. Edelman, Theresa Albergo, Geoffrey Moodie, Paul Martakos, Abraham R. Tzafriri, Renu Virmani, Scott Corbeil, Suzanne Conroy, Keith M. Faucher, Natalie Artzi |
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| Přispěvatelé: | Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Harvard University--MIT Division of Health Sciences and Technology, Artzi, Natalie, Tzafriri, Abraham R., Edelman, Elazer R. |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Drug Swine media_common.quotation_subject medicine.medical_treatment 0206 medical engineering Biomedical Engineering 02 engineering and technology 030204 cardiovascular system & hematology engineering.material Pharmacology Article 03 medical and health sciences 0302 clinical medicine Coated Materials Biocompatible Coating Fatty Acids Omega-3 Materials Testing Coronary stent medicine Animals cardiovascular diseases media_common Sirolimus business.industry Models Cardiovascular Stent medicine.disease equipment and supplies 020601 biomedical engineering Resorption Coronary arteries Stenosis medicine.anatomical_structure surgical procedures operative engineering Rabbits business medicine.drug |
| Zdroj: | Springer US |
| Popis: | The long held assumption that sustained drug elution from stent coatings over weeks to months is imperative for clinical efficacy has limited the choice for stent coating materials. We developed and evaluated an omega-3 fatty acid (O3FA) based stent coating that is 85% absorbed and elutes 97% of its Sirolimus analog (Corolimus) load within 8d of implantation. O3FA coated stents sustained drug levels in porcine coronary arteries similarly to those achieved by slow-eluting durable coated Cypher Select Plus Stents and with significantly lower levels of granuloma formation and luminal stenosis. Computational modeling confirmed that diffusion and binding constants of Corolimus and Sirolimus are identical and explained that the sustained retention of Corolimus was facilitated by binding to high affinity intracellular receptors (FKBP12). First in man outcomes were positive—unlike Cypher stents where late lumen loss drops over 6 month, there was a stable effect without diminution in the presence of O3FA. These results speak to a new paradigm whereby the safety of drug eluting stents can be optimized through the use of resorbable biocompatible coating materials with resorption kinetics that coincide with the dissociation and tissue elimination of receptor-bound drug. National Institutes of Health (U.S.) (R01 GM-49039) |
| Databáze: | OpenAIRE |
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