Biomedical Engineering Reference
In-Depth Information
a
b
100
0.3
t
e
= 2 days
t
e
= 18 days
t
e
= 3 months
80
0.2
60
40
0.1
20
0
0
0
1
2
3
4
0
1
2
3
4
time (weeks)
time (weeks)
Fig. 6
Sensitivity analysis of the medial layer phase-change model to the characteristic polymer
emptying time scale
t
e
. Temporal evolution of
a
the liquid-phase drug concentration
c
0
;
b
the bound
drug concentration
c
b
, each time averaged over the entirety of their respective layers
time steps (especially at the beginning of the simulation) which for our numerical
method would lead to longer overall calculation times in the case of the single-phase
model compared to the two-phase model. The two-phase model avoids these large
gradients, since the initial drug is entirely stored in the solid phase at the initial time
step, which is not in contact with the wall.
Our previous research has shown that a simplified one-phase model in the wall
(assuming instantaneous drug reaction and thus a constant partition of bound and free
drug) cannot capture accurately the drug dynamics [
15
]: neither drug accumulation
nor drug residence time can be accurately predicted with a one-phase model.
The present results highlight how the release kinetics in the polymer and the drug
dynamics in the wall are highly and nonlinearly coupled. The goal of controlled drug
release is to obtain and to maintain sufficiently high drug concentrations in the wall
so as to keep their therapeutic effectiveness over an extended period of time. The
present work shows that the drug release, controlled by
t
0
and
ʵ
0
(other than
D
0
),
needs to be tailored to the specific drug kinetics in the arterial wall in order to reach
optimal DES performance.
Acknowledgments
Franz Bozsak is supported by a grant from the LaSIPS Laboratory of Excel-
lence. This work is supported in part by a permanent endowment in Cardiovascular Cellular
Engineering from the AXA Research Fund (to Abdul I. Barakat) and by the MIUR-CNR project
“Interomics”, 2014 (to Giuseppe Pontrelli).
References
1. Tzafriri, A.R., Groothuis, A., Price, G.S., Edelman, E.R.: Stent eluting rate determines drug
deposition and receptor-mediated effects. J. Controlled Release
161
, 918-926 (2012)
2. Tesfamariam, B.: Drug release kinetics from stent device-based delivery systems. J. Cardiovasc.
Pharmacol.
51
(2), 118-125 (2008)
3. Venkatraman, S., Boey, F.: Release profiles in drug-eluting stents: issues and uncertainties. J.
Control. Release
120
(3), 149-160 (2007)
