Nanotechnology and nanomedicine in cardiovascular therapy - Biomaterials and Devices for the Circulatory System - page 247

subcutaneous and intraperitoneal injection (Cohen-sela et al. , 2006a,b).
These agents may provide a cost-effective alternative.
In addition to improving drug delivery, advances in nanotechnology may
also modify drug action. Superparamagnetic nanoparticles can render
endothelial cells magnetically responsive and thereby guide them onto steel
stent wires through a series of magnetic fi eld gradients (Polyak et al. , 2008).
Nanoparticles as gene carriers have been implicated as possible therapeutic
agents. A poly(lactic-co-glycolic acid) complex with an incorporated
plasmid DNA shows reduced interactions with blood components when
infused into a rabbit carotid artery. When these particles are loaded with
antisense against monocyte chemotactic protein-1, an improvement in gene
transfer into vascular lesions was observed with a reduction of the
intima : media ratio (Yang et al. , 2008).

9.1.2 Angiogenesis

Angiogenesis is the foundation of new blood vessels and may be due to
vasculogenesis (spontaneous blood formation) or intussusception (growth
of new blood vessels by branching from existing ones) (Burri et al. , 2004).
Therapeutic angiogenesis is used to promote healing in conditions which
were traditionally diffi cult to treat, such as ischemic ulceration. Vascular
endothelial cell growth factor (VEGF) is a key component in promoting
angiogenesis, but intravenous administration alone is ineffective and
localised delivery is required. This was originally described using a peripher-
ally inserted catheter which is invasive. VEGF bound to dextran sulphate
at its heparin binding site and encapsulated by selected polycations (chito-
san, polyethylenimine, or poly-L-lysine) can produce controlled local release
of VEGF for approximately 10 days (Huang et al. , 2007). VEGF incorpo-
rated into a hydrogel is stable for up to a month (Matsusaki et al. , 2007).
VEGF-gene delivery when combined with nanoparticles is an alternative
to protein delivery. When injected into rabbit myocardium the enhanced
gene transfection produces a signifi cant increase in the number of capillar-
ies (Yi et al. , 2006). In addition a similar agent injected into a rat ischaemic
limb model demonstrated a signifi cant improvement in neovascularisation
in comparison to plasmid DNA at 12 days following therapy (Kang et al. ,
2008). Furthermore, magnetic nanoparticles containing VEGF plasmid can
be localised to a specifi c area when in a magnetic fi eld producing enhanced
VEGF delivery and a subsequent doubling of the capillary density and
capillary-to-muscle fi bre ratio when compared with controls (Jiang et al. ,
2005).
In addition, local expression of VEGF can be induced by targeting
hypoxia inducible factors such as hypoxia inducible factor-1

￿ ￿ ￿ ￿ ￿

α . When

nanoparticles containing the hypoxia inducible factor-1 α gene are applied