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Research Papers

Modeling and Analysis of Drug-Eluting Stents With Biodegradable PLGA Coating: Consequences on Intravascular Drug Delivery

[+] Author and Article Information
Xiaoxiang Zhu

Department of Chemical Engineering,
Massachusetts Institute of Technology,
77 Massachusetts Avenue,
Room 66-060,
Cambridge, MA 02139
e-mail: zhuxx@mit.edu

Richard D. Braatz

Department of Chemical Engineering,
Massachusetts Institute of Technology,
77 Massachusetts Avenue,
Room 66-548,
Cambridge, MA 02139
e-mail: braatz@mit.edu

1Corresponding author.

Manuscript received April 18, 2014; final manuscript received July 26, 2014; accepted manuscript posted August 1, 2014; published online September 4, 2014. Assoc. Editor: Ram Devireddy.

J Biomech Eng 136(11), 111004 (Sep 04, 2014) (10 pages) Paper No: BIO-14-1169; doi: 10.1115/1.4028135 History: Received April 18, 2014; Revised July 26, 2014; Accepted August 01, 2014

Increasing interests have been raised toward the potential applications of biodegradable poly(lactic-co-glycolic acid) (PLGA) coatings for drug-eluting stents in order to improve the drug delivery and reduce adverse outcomes in stented arteries in patients. This article presents a mathematical model to describe the integrated processes of drug release in a stent with PLGA coating and subsequent drug delivery, distribution, and drug pharmacokinetics in the arterial wall. The integrated model takes into account the PLGA degradation and erosion, anisotropic drug diffusion in the arterial wall, and reversible drug binding. The model simulations first compare the drug delivery from a biodegradable PLGA coating with that from a biodurable coating, including the drug release profiles in the coating, average arterial drug levels, and arterial drug distribution. Using the model for the PLGA stent coating, the simulations further investigate drug internalization, interstitial fluid flow in the arterial wall, and stent embedment for their impact on drug delivery. Simulation results show that these three factors, while imposing little change in the drug release profiles, can greatly change the average drug concentrations in the arterial wall. In particular, each of the factors leads to significant and yet distinguished alterations in the arterial drug distribution that can potentially influence the treatment outcomes. The detailed integrated model provides insights into the design and evaluation of biodegradable PLGA-coated drug-eluting stents for improved intravascular drug delivery.

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Figures

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Fig. 1

(a) Cross-sectional view of an implanted stent in a coronary artery. (b) Schematic of a single stent strut with PLGA coating half-embedded into the arterial wall. Cartesian coordinate (x, y) and cylindrical coordinate (r, θ) are both illustrated.

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Fig. 2

Illustrated mesh of the model domain. (The actual mesh used in simulation is much finer).

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Fig. 3

Percentage relative error of different mesh sizes compared with the extremely fine reference mesh. (a) Varying mesh size in the arterial wall with constant mesh size of 1 μm in the coating; and (b) varying mesh size in the coating with constant mesh size of 5 μm in the arterial wall.

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Fig. 4

Comparison of simulated drug release profiles for the PLGA stent coating (solid) and the biodurable coating (dashed). (Half strut embedment, ki = 0, and vr = 0).

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Fig. 5

Spatially averaged concentrations of free drug and bound drug in the arterial wall for the PLGA coating case and the biodurable coating case. (Half strut embedment, ki = 0, and vr = 0).

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Fig. 6

Drug concentration distribution in the arterial wall at 25 days for intravascular drug delivery from a PLGA stent coating. Color bar is in logarithmic scale (mol/m3). (Half strut embedment, ki = 0, and vr = 0).

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Fig. 7

Average concentrations of free drug, bound drug, and internalized drug in the arterial wall for a relatively small internalization rate constant. (Half strut embedment, vr = 0, and ki = 10-4kd).

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Fig. 8

Average concentrations in the arterial wall for internalized drug (a) and bound drug (b) at different internalization rates. (Half strut embedment and vr = 0).

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Fig. 9

Arterial drug distribution at 25 days for (a) small internalization rate ki = 10-4kd, and (b) fast internalization rate ki = 10-2kd. Color bar is in logarithmic scale (mol/m3). (Half strut embedment and vr = 0).

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Fig. 10

The average drug concentrations in the arterial evolution at different interstitial fluid flow velocities. (Half strut embedment and ki = 0).

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Fig. 11

Arterial drug distributions for free drug and bound drug with transmural interstitial flow (v = 0.01 μm/s) at day 20. Color bar is in logarithmic scale (mol/m3). (Half strut embedment and ki = 0).

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Fig. 12

The average bound drug levels in the arterial wall for different strut embedment (ki = 0 and vr = 0)

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Fig. 13

Bound drug distribution in the arterial wall at day 25 for (a) a contacting stent strut, (b) a half-embedded strut, and (c) a fully embedded strut. Color bar is in logarithmic scale (mol/m3). (ki = 0, and vr = 0).

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