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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

Contour plots of the effect of the presence of SMCs in the SES on the cost function for paclitaxel (left column) and sirolimus (right column) over the design space consisting of initial concentration in the stent polymerc0 and release timetE.The scale for the cost function representation is truncated at a maximum of 1; all values larger than 1 are colored black. The green contour line traces , the yellow contour line , and the red contour line . The horizontal axis at the top of the plot marks the time points of 1 (h)our, 1 (d)ay, 1 (w)eek, 1 (m)onth and 1 (y)ear. Gray dots indicate evaluated designs. Optimization cases A: paclitaxel release and B: sirolimus release with SES SMC density corresponding to 1% of the medial SMC density. C: Paclitaxel release and D: sirolimus release with SES SMC density corresponding to 5% of the medial SMC density. E: Paclitaxel release and F: sirolimus release with SES SMC density corresponding to 25% of the medial SMC density.
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pone.0130182.g008: Contour plots of the effect of the presence of SMCs in the SES on the cost function for paclitaxel (left column) and sirolimus (right column) over the design space consisting of initial concentration in the stent polymerc0 and release timetE.The scale for the cost function representation is truncated at a maximum of 1; all values larger than 1 are colored black. The green contour line traces , the yellow contour line , and the red contour line . The horizontal axis at the top of the plot marks the time points of 1 (h)our, 1 (d)ay, 1 (w)eek, 1 (m)onth and 1 (y)ear. Gray dots indicate evaluated designs. Optimization cases A: paclitaxel release and B: sirolimus release with SES SMC density corresponding to 1% of the medial SMC density. C: Paclitaxel release and D: sirolimus release with SES SMC density corresponding to 5% of the medial SMC density. E: Paclitaxel release and F: sirolimus release with SES SMC density corresponding to 25% of the medial SMC density.

Mentions: Unlike healthy arteries, atherosclerotic vessels contain SMCs in the SES. The presence of SMCs in the SES alters drug transport within this layer and necessitates the incorporation of drug reaction with the SMCs in the SES. Fig 8 depicts the optimization results for paclitaxel and sirolimus for progressively increasing fractions of SMCs in the SES, expressed as a percentage of the SMC volume fraction in the media.


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)

Contour plots of the effect of the presence of SMCs in the SES on the cost function for paclitaxel (left column) and sirolimus (right column) over the design space consisting of initial concentration in the stent polymerc0 and release timetE.The scale for the cost function representation is truncated at a maximum of 1; all values larger than 1 are colored black. The green contour line traces , the yellow contour line , and the red contour line . The horizontal axis at the top of the plot marks the time points of 1 (h)our, 1 (d)ay, 1 (w)eek, 1 (m)onth and 1 (y)ear. Gray dots indicate evaluated designs. Optimization cases A: paclitaxel release and B: sirolimus release with SES SMC density corresponding to 1% of the medial SMC density. C: Paclitaxel release and D: sirolimus release with SES SMC density corresponding to 5% of the medial SMC density. E: Paclitaxel release and F: sirolimus release with SES SMC density corresponding to 25% of the medial SMC density.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0130182.g008: Contour plots of the effect of the presence of SMCs in the SES on the cost function for paclitaxel (left column) and sirolimus (right column) over the design space consisting of initial concentration in the stent polymerc0 and release timetE.The scale for the cost function representation is truncated at a maximum of 1; all values larger than 1 are colored black. The green contour line traces , the yellow contour line , and the red contour line . The horizontal axis at the top of the plot marks the time points of 1 (h)our, 1 (d)ay, 1 (w)eek, 1 (m)onth and 1 (y)ear. Gray dots indicate evaluated designs. Optimization cases A: paclitaxel release and B: sirolimus release with SES SMC density corresponding to 1% of the medial SMC density. C: Paclitaxel release and D: sirolimus release with SES SMC density corresponding to 5% of the medial SMC density. E: Paclitaxel release and F: sirolimus release with SES SMC density corresponding to 25% of the medial SMC density.
Mentions: Unlike healthy arteries, atherosclerotic vessels contain SMCs in the SES. The presence of SMCs in the SES alters drug transport within this layer and necessitates the incorporation of drug reaction with the SMCs in the SES. Fig 8 depicts the optimization results for paclitaxel and sirolimus for progressively increasing fractions of SMCs in the SES, expressed as a percentage of the SMC volume fraction in the media.

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