Coronary Angioplasty and Drug-Eluting Stents - Applications of Biotechnology in Cardiovascular Therapeutics - page 279

of PEG-based block copolymer encapsulating doxorubicin. It accumulates in
vascular lesions with increased permeability. In a balloon injury model of the rat
carotid artery, intravenous administration of NK911 significantly inhibited the
neointimal formation. The effect of NK911 was due to inhibition of vascular
smooth muscle proliferation but not to enhancement of apoptosis or inhibition of
inflammatory cell recruitment. NK911 was well tolerated without any adverse sys-
temic effects. These results suggest that nanoparticle technology is a promising and
safe approach to target vascular lesions with increased permeability for the preven-
tion of restenosis after balloon injury. Coroxane ™ (Abraxis), a nanoparticulate
microtubule stabilizer, is in phase II clinical trials in conjunction with angioplasty/
stents to prevent arterial restenosis.
Biomedical engineers at Purdue University (Lafayette, IN) have shown that vas-
cular stents used to repair arteries might perform better if their surfaces contained
“nano-bumps” that mimic tiny features found in living tissues. The stents, which are
made of titanium and other metals, enable the arteries to grow new tissue after
vessel-clogging plaque deposits have been removed. A major problem, however, is
that the body often perceives the metal devices as foreign invaders, hindering
endothelial cells from attaching to the scaffolding and prompting the creation of
scar tissue, which can build up inside blood vessels and interfere with blood flow.
If a stent does not attach firmly it can become loose, and parts of it will actually
break off and go down the bloodstream. There is need for new materials that cause
the endothelial cells to attach better to these stents without creating as much danger-
ous scar tissue. The researchers tested discs of titanium containing surface bumps
about as wide as 100 nm. The metals used to make conventional stents have features
about ten times larger or none at all. The nanometer-scale bumps mimic surface
features of proteins and natural tissues, prompting cells to stick better. Ideally,
endothelial cells should quickly attach to stents and form a coating only one cell
layer thick. The researchers found that nearly three times as many cells stuck to the
discs containing the nanobumps, as compared to ordinary titanium. Further research
is planned that will replace the titanium disks with tube-shaped pieces of the nano-
featured metal, which will resemble the actual shape of real stents.
Currently available stents have problems with imaging within the stent structure,
where potential restenosis can occur. Biophan Technologies Inc has two solutions
for stent visibility: a thin-film nanomagnetic particle coating solution and an anti-
antenna solution. These solutions enable the noninvasive, MRI-based, imaging of
these devices which today can only be accomplished through more complicated
invasive procedures. These approaches will become an important part of the rapidly
growing worldwide market for stents and vascular implants.
By using antiproliferative compounds that elute from the surface of a stent, the
latest generation of stents has enabled a significant reduction in restenosis rates,
that is, when there is a renarrowing of the vessel after stent implantation.
Nanocarrier-based delivery presents a viable alternative to the current stent-based
therapies (Brito and Amiji 2007 ; Feng et al. 2007 ; Margolis et al. 2007 ).
NOLabs is developing NO-eluting nanofibers. One potential application is
incorporation into stents for antithrombogenic action. NO has vasodilating action
as well, which may be beneficial in ischemic heart disease.