Biomedical Engineering Reference
In-Depth Information
suggest that this inhibition of proliferation had a minimal effect on apop-
tosis (Kapadia
et al.
, 2008).
Platelet-derived growth factor (PDGF) is a key component in vein graft
failure as it promotes proliferating vascular smooth muscle cells prolifera-
tion and monocyte infi ltration. Therefore, delivery of PDGF-receptor
tyrosine kinase inhibitor may inhibit hyperplasia. Indeed, polyethylene-
glycol-modifi ed poly(DL-lactide-coglycolide) nanoparticles coated with a
PDGF-receptor tyrosine kinase inhibitor have been investigated. These
particles were infused into excised rabbit segments of jugular vein and
subsequently interposed into the ipsilateral carotid. At 28 days, there was
signifi cant suppression of neointima formation when compared to controls
(Kimura
et al.
, 2008).
Doxorubicin, an alternative antiproliferative drug, has also been coupled
with polyethylene glycol (PEG)-based block copolymer to form a core-
shell nanoparticle (NK911). Again, intravenous administration of NK911
signifi cantly inhibited neointima formation in a rat carotid model 4 weeks
post-injury. Intravenous doxorubicin alone did not produce such results.
Again an important observation is that NK911 inhibition of vascular smooth
muscle proliferation is not accompanied by apoptosis or inhibition of
infl ammatory cell recruitment. Furthermore, NK911 was well tolerated
without any adverse systemic effects (Uwatoku
et al.
, 2003).
A balance between limiting vascular stenosis and promoting endothelial
healing in these balloon injury models is critical. The ability of nanoparticles
to achieve this balance is demonstrated by the use of
α
v
β
3
-integrin-targeted
rapamycin. Injured rabbit femoral arteries using a balloon stretch model
showed a 50% reduction in luminal plaque in the targeted rapamycin seg-
ments when compared with contralateral control vessels using magnetic
resonance angiograms (MRA). Indeed endothelial healing was similar in
the
3
-integrin-targeted rapamycin treated group as in controls (Cyrus
et al.
, 2008).
Other more commonly used agents have been combined with nanoscaf-
folds to investigate any improvement in bioavailability. Prednisolone-
phosphate incorporated in pegylated 3,5-dipentadecyloxybenzamidine
hydrochloride (TRM-484) has been shown to signifi cantly reduce in-stent
neointimal growth in atherosclerotic rabbits (Joner
et al.
, 2008). Lisinopril
encapsulated in poly(lactide-co-glicolide) nanoparticles has shown a
promising release profi le suggesting that it may be suitable for site-specifi c
delivery by catheters in the prevention of restenosis following balloon
angioplasty (Varshosaz and Soheili, 2008). 2-(2-Aminopyrimidino) ethyl-
diene-1,1bisphosphonic acid incorporated into a polylactide/glycolide-
based polymer again produces a signifi cant attenuation of neointima : media
ratio (40%) and stenosis (45%) in a rat carotid artery injury model in
comparison with controls. Hyperplasia was also signifi cantly reduced after
α
β
v
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