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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November 2014
Research-Article
Modeling and Analysis of Drug-Eluting Stents With Biodegradable PLGA Coating: Consequences on Intravascular Drug Delivery
Xiaoxiang Zhu,
Xiaoxiang Zhu
Department of Chemical Engineering,
77 Massachusetts Avenue,
Room 66-060,
e-mail: zhuxx@mit.edu
Massachusetts Institute of Technology
,77 Massachusetts Avenue,
Room 66-060,
Cambridge, MA 02139
e-mail: zhuxx@mit.edu
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Richard D. Braatz
Richard D. Braatz
1
Department of Chemical Engineering,
77 Massachusetts Avenue,
Room 66-548,
e-mail: braatz@mit.edu
Massachusetts Institute of Technology
,77 Massachusetts Avenue,
Room 66-548,
Cambridge, MA 02139
e-mail: braatz@mit.edu
1Corresponding author.
Search for other works by this author on:
Xiaoxiang Zhu
Department of Chemical Engineering,
77 Massachusetts Avenue,
Room 66-060,
e-mail: zhuxx@mit.edu
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,
77 Massachusetts Avenue,
Room 66-548,
e-mail: braatz@mit.edu
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. Nov 2014, 136(11): 111004 (10 pages)
Published Online: September 4, 2014
Article history
Received:
April 18, 2014
Revision Received:
July 26, 2014
Accepted:
August 1, 2014
Citation
Zhu, X., and Braatz, R. D. (September 4, 2014). "Modeling and Analysis of Drug-Eluting Stents With Biodegradable PLGA Coating: Consequences on Intravascular Drug Delivery." ASME. J Biomech Eng. November 2014; 136(11): 111004. https://doi.org/10.1115/1.4028135
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