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Optimization of Drug Delivery by Drug-Eluting Stents.

Bozsak F, Gonzalez-Rodriguez D, Sternberger Z, Belitz P, Bewley T, Chomaz JM, Barakat AI - PLoS ONE (2015)

Bottom Line: However, late stent thrombosis remains a safety concern in DES, mainly due to delayed healing of the endothelial wound inflicted during DES implantation.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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire d'Hydrodynamique (LadHyX), École Polytechnique-CNRS, Palaiseau cedex, France.

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.

No MeSH data available.


Related in: MedlinePlus

Flow diagram of the optimization algorithm and its coupling to the computational model.
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pone.0130182.g004: Flow diagram of the optimization algorithm and its coupling to the computational model.

Mentions: The optimization procedure (Fig 4) begins with the evaluation of a set of initial sampling points to create the very first surrogate surface. We use the latin hypercube sampling algorithm presented in [60] to ensure a uniform distribution of these points throughout the design space. We use 20 initial designs for our 2-dimensional design space.


Optimization of Drug Delivery by Drug-Eluting Stents.

Bozsak F, Gonzalez-Rodriguez D, Sternberger Z, Belitz P, Bewley T, Chomaz JM, Barakat AI - PLoS ONE (2015)

Flow diagram of the optimization algorithm and its coupling to the computational model.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4470631&req=5

pone.0130182.g004: Flow diagram of the optimization algorithm and its coupling to the computational model.
Mentions: The optimization procedure (Fig 4) begins with the evaluation of a set of initial sampling points to create the very first surrogate surface. We use the latin hypercube sampling algorithm presented in [60] to ensure a uniform distribution of these points throughout the design space. We use 20 initial designs for our 2-dimensional design space.

Bottom Line: However, late stent thrombosis remains a safety concern in DES, mainly due to delayed healing of the endothelial wound inflicted during DES implantation.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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire d'Hydrodynamique (LadHyX), École Polytechnique-CNRS, Palaiseau cedex, France.

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.

No MeSH data available.


Related in: MedlinePlus