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Sustained Efficacy and Arterial Drug Retention by a Fast Drug Eluting Cross-Linked Fatty Acid Coronary Stent Coating
- Source :
- Springer US
- Publication Year :
- 2015
- Publisher :
- Springer US, 2015.
-
Abstract
- 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.<br />National Institutes of Health (U.S.) (R01 GM-49039)
- Subjects :
- 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
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Springer US
- Accession number :
- edsair.doi.dedup.....8e6709284f66e8c3435b08cef778da66