Biomedical Engineering Reference
In-Depth Information
poly(
n
-butyl methacrylate) [PBMA]) containing 140
μ
g/cm
2
sirolimus (Kukreja et al., 2008).
The paclitaxel-eluting TAXUS
TM
stent (Boston Scientific, Natick, MA) incorporates a stain-
less steel platform with a nonerodible polymer coating (polystyrene-
b
-isobutylene-
b
-
styrene [SIBS]) combined with 100
μ
g/cm
2
of paclitaxel (Kukreja et al., 2008). The strength
of the nonerodible polymers in both CYPHER and TAXUS stents lies in their ability to pre-
vent restenosis in a diverse range of patients. However, both cause significant delay in arte-
rial healing manifested by persistent fibrin deposition and poor endothelialization when
compared to instances of bare metal stent implantation (Finn et al., 2007). Consequently,
more biocompatible matrix materials have been introduced. These include the nonerodible
phosphorylcholine (PC) and erodible polyesters such as PLGA, PLA, poly-l-lactide (PLLA),
and poly-d,l-lactide (PDLLA) (Raval et al., 2007).
Nonerodible Polymeric Matrix
The market for commercially available DES is currently dominated by stents with nonerod-
ible polymer matrices (Kukreja et al., 2008; Fishell et al., 2009). Table 6.1 shows the DES
drug delivery systems using these matrices. Phosphorylcholine is the only natural poly-
mer among a number of synthetic polymers that have proven track records in stenting
applications.
Polymer Blends
The CYPHER sirolimus-eluting coronary stent (CYPHER stent) is a combination product
comprising two regulated components: a device (a stent system) and a drug product (a
formulation of sirolimus in a polymer coating). The CYPHER stent was the first DES to
receive both the Conformité Européenne (CE) mark and FDA approval in April 2002 and
2003, respectively (Daemen and Serruys, 2007). The stent, under the name of Bx Velocity
(manufactured by Cordis Corporation/Johnson & Johnson), is used to treat lesions 30 mm
in length or smaller and with a reference diameter of 2.25-4 mm. The stent material is
electropolished stainless steel (316L), laser cut from seamless tubing in a sinusoidal pat-
tern. The designed strut thickness is 140
μ
m (Nakazawa et al., 2009). The usable length
of the stent placement system is either 145 cm for RAPTOR™ over-the-wire or 137 cm for
RAPTORRAIL
®
Rapid Exchange. Polymer blend PEVA/PBMA is used as the matrix mate-
rial for loading sirolimus, which it achieves using a mixture at a ratio of 67% polymer and
33% sirolimus. The molecular formula of sirolimus is C
51
H
79
NO
13
with a molecular weight
of 914.2 g/mol and is contained within the drug reservoir layer at a density of 140
μ
g/cm
2
,
80% of which is released in 30 days (Kukreja et al., 2008).
PEVA and PBMA have proven track records as controlled release polymers (Rhodes
and Porter, 1998). PEVA (Figure 6.2) is produced by copolymerization of ethylene and
vinyl acetate (VA). With increasing proportion of the polar comonomer VA, the products
change from modified polyethylene to a rubberlike product. Commercially available PEVA
TABLE 6.1
DES Drug Delivery Systems Using a Nonerodible Polymer Matrix
StentDesign
Drug(Dose)
Matrix(Ratio)
Manufacturer
Cypher
Sirolimus (1.4
μ
g/mm
2
)
PEVA + PBMA
Cordis
Taxus
Paclitaxel (1.0
μ
g/mm
2
)
SIBS (Translute)
Boston Scientific
Xience V
Everolimus (1.0
μ
g/mm
2
)
Fluoropolymer
Abbott Vascular
Endeavor
Zotarolimus (1.6
μ
g/mm
2
)
Phosphorylcholine
Medtronic
