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

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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Assessment of a mathematical model considering the effect of flow rate on in-vitro drug-release from PLGA films

E3S Web of Conferences ◽

10.1051/e3sconf/202132104011 ◽

2021 ◽

Vol 321 ◽

pp. 04011

Author(s):

Navideh Abbasnezhad ◽

Farid Bakir ◽

Stéphane Champmartin ◽

Mohammadali Shirinbayan

Keyword(s):

Mathematical Model ◽

Drug Release ◽

Flow Rate ◽

Drug Carrier ◽

Diclofenac Sodium ◽

Drug Eluting Stents ◽

In Vitro Drug Release ◽

Drug Eluting ◽

Release Profiles

Drug-eluting stents implanted in blood vessels are subject to various dynamics of blood flow. In this study, we present the evaluation of a mathematical model considering the effect of flow rate, to simulate the kinetic profiles of drug release (Diclofenac Sodium (DS)) from in-vitro from PLGA films. This model solves a set of non-linear equation for modeling simultaneously the burst, diffusion, swelling and erosion involved in the mechanisms of liberation. The release parameters depending on the flow rate are determined using the corresponding mathematical equations. For the evaluation of the proposed model, test data obtained in our laboratory are used. To quantify DS release from drug-carrier PLGA films, we used the flow-through cell apparatus in a closed-loop. Four flow rate values are applied. For each value, the model-substance liberation kinetics showed an increase in drug released with the flow rate. The simulated release profiles show good agreement with the experimental results. Therefore, the use of this model could provide a practical tool to assess in-vitro drug release profiles from polymer matrices under continuous flow rate constraint, and could help improve the design of drug eluting stents.

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Modeling Drug Eluting Stents for Coronary Artery Bifurcation Considering Non-Newtonian Effects

ASME 2010 3rd Joint US-European Fluids Engineering Summer Meeting: Volume 1, Symposia – Parts A, B, and C ◽

10.1115/fedsm-icnmm2010-31190 ◽

2010 ◽

Author(s):

Marjan Molavi Zarandi ◽

Rosaire Mongrain ◽

Olivier F. Bertrand

Keyword(s):

Arterial Wall ◽

Drug Eluting Stents ◽

Drug Eluting Stent ◽

Simulation Techniques ◽

Drug Concentrations ◽

Conventional Drug ◽

Computational Fluid Dynamics Analysis ◽

Stent Strut ◽

Drug Eluting ◽

Stenotic Arteries

Drug Eluting Stents (DES) are commonly used for the treatment of stenotic arteries. Restenosis can be treated by delivering anti-thrombotic and anti-proliferative drugs to the arterial wall. The main mechanism of the drug eluting stent is to allow diffusion of the drug from the coating on the stent, into the arterial wall over a prolonged period of time. Investigation of blood flow hemodynamics and shear stress are of great importance in understanding the transport of drugs through the circulatory systems and predicting the performance of drug eluting stents. While drug eluting stent effectively reduces restenosis rate, the conventional drug eluting stent should be optimized to be used in the bifurcation stenting. Various flow patterns due to specific designs of drug eluting stent influence drug delivery. Numerical simulation techniques are appropriate approaches to study such phenomena which can be used to optimize the design of drug eluting stents for bifurcations. In this paper, the complexity of drug eluting stent function in the bifurcation is presented by employing computational fluid dynamics analysis for various stent strut designs. Drug transportation through the lumen and determination of local drug concentrations in arterial wall is carried out for both Newtonian and non-Newtonian flow conditions. It is, to the author’s best knowledge, the first investigation of drug dispersion in arterial bifurcation considering the effects of both the blood rheological properties and stent strut design.

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How does vessel curvature influence drug release from DES and drug transport in arterial tissue?

Jornada de Jóvenes Investigadores del I3A ◽

10.26754/jji-i3a.003610 ◽

2019 ◽

Vol 7 ◽

Author(s):

Javier Escuer Gracia ◽

Estefanía Peña ◽

Irene Aznar ◽

Miguel Ángel Martínez

Keyword(s):

Blood Flow ◽

Drug Release ◽

Drug Transport ◽

Computational Models ◽

Arterial Wall ◽

Drug Eluting Stents ◽

Complex Geometries ◽

Arterial Tissue ◽

Drug Eluting ◽

Vessel Curvature

Several computational models of transport of drugs eluted from drug-eluting stents (DES) in curved arteries were developed in order to investigate the influence of the arterial curvature and complex geometries on drug transport in the blood flow and in the arterial wall.

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ANISOTROPIC TRANSPORT THROUGH POLYMER LAYER AND POROUS ARTERIAL WALL WITH BINDING IN DRUG-ELUTING STENTS USING THE FEM

10.26678/abcm.encit2018.cit18-0509 ◽

2018 ◽

Author(s):

fabiane aparecida dos santos frazzoli ◽

Rachel Manhaes de Lucena ◽

Norberto Mangiavacchi ◽

José da Rocha Miranda Pontes ◽

Gustavo Rabello dos Anjos ◽

...

Keyword(s):

Arterial Wall ◽

Polymer Layer ◽

Drug Eluting Stents ◽

Drug Eluting ◽

Anisotropic Transport

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Influence of Elongation of Paclitaxel-Eluting Electrospun-Produced Stent Coating on Paclitaxel Release and Transport Through the Arterial Wall after Stenting

Polymers ◽

10.3390/polym13071165 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1165

Author(s):

Zhanna K. Nazarkina ◽

Boris P. Chelobanov ◽

Konstantin A. Kuznetsov ◽

Alexey V. Shutov ◽

Irina V. Romanova ◽

...

Keyword(s):

Drug Release ◽

Arterial Wall ◽

Release Kinetics ◽

Artery Wall ◽

Vascular Stents ◽

Drug Eluting ◽

Fiber Breaks ◽

Stent Diameter ◽

Stent Coating

It was previously shown that polycaprolactone (PCL)-based electrospun-produced paclitaxel (PTX)-enriched matrices exhibit long-term drug release kinetics and can be used as coatings for drug-eluting stents (DES). The installation of vascular stents involves a twofold increase in stent diameter and, therefore, an elongation of the matrices covering the stents, as well as the arterial wall in a stented area. We studied the influence of matrix elongation on its structure and PTX release using three different electrospun-produced matrices. The data obtained demonstrate that matrix elongation during stent installation does not lead to fiber breaks and does not interfere with the kinetics of PTX release. To study PTX diffusion through the expanded artery wall, stents coated with 5%PCL/10%HSA/3%DMSO/PTX and containing tritium-labeled PTX were installed into the freshly obtained iliac artery of a rabbit. The PTX passing through the artery wall was quantified using a scintillator β-counter. The artery retained the PTX and decreased its release from the coating. The retention of PTX by the arterial wall was more efficient when incubated in blood plasma in comparison with PBS. The retention/accumulation of PTX by the arterial wall provides a prolonged drug release and allows for the reduction in the dose of the drugs in electrospun-produced stent coatings.

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