Nanotechnology and nanomedicine in cardiovascular therapy - Biomaterials and Devices for the Circulatory System - page 245

controlled release of an antiproliferative agent, e.g Paclitaxel, following
deployment and so improve long-term patency rates (Saia et al. , 2008).
However, this technology has drawbacks including stent thrombosis, long-
term anti-platelet therapy and expense. The delivery of Paclitaxel using
nanoscaffolds may improve patency rates even further. Nab-paclitaxel, a
novel form of albumin-bound paclitaxel has been shown to reduce resteno-
sis in animals and its safety is currently being investigated in humans.
Margolis et al. (2007) assessed 23 patients (mean age 66 10 years, 74%

men, 26% with diabetes) receiving various intravenous doses of nab-pacl-
itaxel following stenting of a single de novo lesion. Interestingly no major
adverse cardiac events were reported at two or six months and only four
incidences of restenoses requiring interventions were seen. However, at the
higher doses of Nab-paclitaxel side-effects including moderate neutropenia,
sensory neuropathy and alopecia were noted.
Invasive catheter-based delivery of paclitaxel-coated nanoparticles may
allow concentrated drug administration. Nanoparticles, consisting of
poly(vinyl alcohol)-graft-poly(lactide-co-glycolide) combined with pacli-
taxel, when administered via a catheter placed in balloon-injured rabbit
iliac arteries show a signifi cant 50% reduction in neointimal area when
compared with controls (0.80

±

± 0.19 mm 2 with paclitaxel nanoparticle

0.6 mm 2 control) (Westedt et al. , 2007). Subse-
quent studies have shown similar outcomes when using paclitaxel-loaded
biodegradable scaffolds in animal models (Mei et al. , 2007, 2009).
Neointimal hyperplasia at venous anastomosis sites in renal access
surgery for dialysis is another area where the use of Paclitaxel has been
assessed. Paclitaxel coated expanded poly(tetrafl uoroethylene) (ePTFE)
has been shown to reduce stenosis rates. However, these stents release the
agent immediately upon revascularisation rather than a delayed or con-
trolled release, which may attenuate restenosis rates. To enable controlled
drug release, pacliataxel loaded poly(lactic-co-glycolic acid) nanoparticles
were coated onto the luminal surface of ePTFE grafts by micro-tube
pumping and spin penetration techniques. This avoided the initial burst
release of the drug following reconstitution of fl ow within the conduit ( in
vitro ) and produced a controlled drug delivery system (Lim et al. , 2007).
The role of numerous other agents bound to nanoparticles has been
investigated including nitiric oxide (NO). Gels consisting of peptide
amphiphile, heparin, and a diazeniumdiolate nitric oxide donor (1-[ N -
(3-aminopropyl)- N -(3-ammoniopropyl)]diazen-1-ium-1,2-diolate (DPTA/
NO) or disodium 1-[(2-carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-
diolate (PROLI/NO) were applied to the periadventitial region of a rat
carotid artery during surgery after endovascular balloon injury. Gels
released nitric oxide locally for four days and resulted in attenuation in the
neointimal hyperplasia response by up to 77%. Importantly, in vivo studies

treated segments vs. 1.58 ±

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