Mechanisms of Tissue Uptake and Retention in Zotarolimus-Coated Balloon Therapy
| Autor: | Stephen D. Pacetti, Alexander Nikanorov, Elazer R. Edelman, Vijaya B. Kolachalama, John Stankus, Joseph W. Franses, Tarek Shazly, Lewis B. Schwartz, Abraham R. Tzafriri, Hugh Q. Zhao |
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| Přispěvatelé: | Harvard University--MIT Division of Health Sciences and Technology, Kolachalama, Vijaya B., Franses, Joseph W., Shazly, Tarek, Tzafriri, Abraham R., Edelman, Elazer R. |
| Rok vydání: | 2013 |
| Předmět: |
Male
Paclitaxel Swine Femoral artery Pharmacology Balloon Article chemistry.chemical_compound Drug Delivery Systems Organ Culture Techniques Pharmacokinetics Physiology (medical) medicine.artery medicine Animals Distribution (pharmacology) Tissue Distribution Arterial wall Zotarolimus Sirolimus business.industry Femoral Artery chemistry Female Cardiology and Cardiovascular Medicine business Angioplasty Balloon Biomedical engineering medicine.drug |
| Zdroj: | PMC |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/circulationaha.113.002051 |
| Popis: | Background—Drug-coated balloons are increasingly used for peripheral vascular disease, and, yet, mechanisms of tissue uptake and retention remain poorly characterized. Most systems to date have used paclitaxel, touting its propensity to associate with various excipients that can optimize its transfer and retention. We examined zotarolimus pharmacokinetics. Methods and Results—Animal studies, bench-top experiments, and computational modeling were integrated to quantify arterial distribution after zotarolimus-coated balloon use. Drug diffusivity and binding parameters for use in computational modeling were estimated from the kinetics of zotarolimus uptake into excised porcine femoral artery specimens immersed in radiolabeled drug solutions. Like paclitaxel, zotarolimus exhibited high partitioning into the arterial wall. Exposure of intimal tissue to drug revealed differential distribution patterns, with zotarolimus concentration decreasing with transmural depth as opposed to the multiple peaks displayed by paclitaxel. Drug release kinetics was measured by inflating zotarolimus-coated balloons in whole blood. In vivo drug uptake in swine arteries increased with inflation time but not with balloon size. Simulations coupling transmural diffusion and reversible binding to tissue proteins predicted arterial distribution that correlated with in vivo uptake. Diffusion governed drug distribution soon after balloon expansion, but binding determined drug retention. Conclusions—A large bolus of zotarolimus releases during balloon inflation, some of which pervades the tissue, and a fraction of the remaining drug adheres to the tissue–lumen interface. As a result, the duration of delivery modulates tissue uptake where diffusion and reversible binding to tissue proteins determine drug transport and retention, respectively. National Institutes of Health (U.S.) (Grant R01 GM-49039) Abbott Vascular |
| Databáze: | OpenAIRE |
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