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• mechanical stability able to withstand the plastic deformation
during stent expansion; and
• ability to protect the drug from degradation during processes such
as sterilisation and during shelf life.
essentially, the desired polymer is one that can provide safe transport of
the drug through the vasculature without drug loss and ensure
controlled drug release. release can be controlled by such factors as
polymer identity, formulation (drug:polymer ratio) and coating
processes. The formulation and coating developed with the desired
release properties have to show mechanical properties capable of
withstanding implantation. in the development of Biolute, from those
polymers meeting the initial screening parameters, the selection was
narrowed to focus on the criteria of biocompatibility as measured by
local tissue responses in pig coronaries; this led to the selection of Poly-
L-Lactidde (PLLA)
4
as the polymer matrix of Biolute. Another benefit of
PLLA is that its slow degradation allows for full control of release kinetics
since the polymer degradation is limited during the drug-elution period,
which is not the case with polymers that degrade more quickly. The
controlled release kinetics obtained with the homogeneous PLLA
polymer matrix also means that orsiro does not need to have any
additional base or top coat, which is often required for other Des
coatings. Another advantage of the prolonged gentle degradation seen
with PLLA is that it minimises the inflammatory response (see
Figure 2
).
After selection of the appropriate polymer, the next critical step in
terms of elution kinetics was ensuring a uniform coating of the
polymer and drug.
5
The homogenous coating of the stent was realised
using a unique coating technique.
The mechanical stability is crucial for carrier systems of Des and
BioLute, due to the high strength of PLLA, is providing very good
properties. The polymer thickness on the abluminal side of the osiro
device is 7.4
m
m, one of the lowest among available Des (see
Figure 3
).
on orsiro, a circumferential coating rather than an abluminal coating
was chosen to ensure that the polymer adheres to the stent platform
even in the areas that face high stress during stent expansion. This,
together with the strong mechanical properties of the polymer matrix
itself, means that the risk of tearing off the coating as a result of stress
during implantation and balloon dilatation is avoided. The highly
biocompatible polymer gently degrades over one to two years, avoiding
increased inflammation and ultimately metabolises into co
2
and h
2
o via
the Krebs cycle. studies in minipigs have shown no residual PLLA and
benign histology at 24 and 36 months. The biocompatible and gentle
degradation is believed to lead to better patient outcomes.
The sirolimus drug load is 1.4
m
g/mm2 and the elution is optimised for
clinical benefit to 12–14 weeks. (see
Figure 4
).
In vivo
studies have
demonstrated that 50 % of the drug is released within 30 days and 80 %
within three months (see
Figure 5
). The elution curve is adapted to the
therapeutic window of the drug and is in line with that of other -limus-
based stents. While studies have noted that -limus drugs as well as
paclitaxel are effective in clinical use, -limus drugs have proved to be
clinically superior with no significant difference between the different -
limus derivatives.
6,7
PRO-Kinetic Energy Stent Platform
The deliverability and mechanical properties of the underlying stent
backbone are known to be key success factor for any Des. To achieve
Drug-eluting Stents
i n T e r V e n T i o n A L c A r D i o L o g y
4
Figure 1: The Orsiro Stent
The iridescent blue–gold colour of the Orsiro stent comes from the passive PROBIO coating,
which passivates the metallic surface of the stent by preventing ion release.
Figure 2: Inflammation Scores after Implantation of
Three Different Coating Matrix Formulations
Durable Polymer A
+Sirolimus
n = 1
Durable Polymer B
+Sirolimus
n = 10
BIOLute*
n = 10
1
0
1.42
1.47
1.03
2
3
Inammation score
* the PLLA and Sirolimus matrix used on Orsiro
The excellent biocompatibility of the BIOlute coating is reflected in a reduced inflammation
score, at 28 days, for the degradable BIOlute matrix in contrast to the systems based on
durable polymers.
Figure 3: Cross-section of the Orsiro Stent Strut
A
B
The cross-section shows an asymmetrical coating with a thicker layer to the abluminal side
(A, 7.4
m
m) and thinner coating on the luminal side (B).