Optimization of Drug Delivery by Drug-Eluting Stents

Franz Bozsak 1 David Gonzalez-Rodriguez 1 Zachary Sternberger 1 Paul Belitz 2 Thomas Bewley 2 Jean-Marc Chomaz 1 Abdul I Barakat 1
1 LadHyX - Laboratoire d'hydrodynamique
2 UCSD - Department of Mechanical and Aerospace Engineering [San Diego]
Abstract : Drug-eluting stents (DES), which release anti-proliferative drugs into the arterial wall in a controlled manner, have drastically reduced the rate of in-stent restenosis and revolutionized the treatment of atherosclerosis. However, late stent thrombosis remains a safety concern in DES, mainly due to delayed healing of the endothelial wound inflicted during DES implantation. We present a framework to optimize DES design such that restenosis is inhibited without affecting the endothelial healing process. To this end, we have developed a computational model of fluid flow and drug transport in stented arteries and have used this model to establish a metric for quantifying DES performance. The model takes into account the multi-layered structure of the arterial wall and incorporates a reversible binding model to describe drug interaction with the cells of the arterial wall. The model is coupled to a novel optimization algorithm that allows identification of optimal DES designs. We show that optimizing the period of drug release from DES and the initial drug concentration within the coating has a drastic effect on DES performance. Paclitaxel-eluting stents perform optimally by releasing their drug either very rapidly (within a few hours) or very slowly (over periods of several months up to one year) at concentrations considerably lower than current DES. In contrast, sirolimus-eluting stents perform optimally only when drug release is slow. The results offer explanations for recent trends in the development of DES and demonstrate the potential for large improvements in DES design relative to the current state of commercial devices.
Type de document :
Article dans une revue
PLoS ONE, Public Library of Science, 2015, 10 (6), pp.e0130182. 〈10.1371/journal.pone.0130182〉
Liste complète des métadonnées

Littérature citée [82 références]  Voir  Masquer  Télécharger
https://hal-polytechnique.archives-ouvertes.fr/hal-01180322
Contributeur : Denis Roura <>
Soumis le : samedi 25 juillet 2015 - 13:37:13
Dernière modification le : jeudi 10 mai 2018 - 02:03:34
Document(s) archivé(s) le : lundi 26 octobre 2015 - 10:15:51

Fichier

pone.0130182.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Collections

X | X-LADHYX | PARISTECH | UNIV-PARIS-SACLAY | X-DEP-MECA

Citation

Franz Bozsak, David Gonzalez-Rodriguez, Zachary Sternberger, Paul Belitz, Thomas Bewley, et al.. Optimization of Drug Delivery by Drug-Eluting Stents. PLoS ONE, Public Library of Science, 2015, 10 (6), pp.e0130182. 〈10.1371/journal.pone.0130182〉. 〈hal-01180322〉

Exporter

BibTeX TEI DC DCterms EndNote

Partager

Métriques

Consultations de la notice

295

Téléchargements de fichiers

204

Contact

support.ccsd.cnrs.fr
hal.support@ccsd.cnrs.fr
Logo CCSD