Biomedical Engineering Reference
In-Depth Information
Antirestenosis Drugs Encapsulated in Biodegradable
Nanoparticles
Local delivery of antiproliferative drugs encapsulated in biodegradable nanoparticles
has shown promise as an experimental strategy for preventing restenosis develop-
ment. A novel PDGFR b-specific tyrphostin, AGL-2043 (Calbiochem), was formu-
lated in polylactide-based nanoparticles and was administered intraluminally to the
wall of balloon-injured rat carotid and stented pig coronary arteries (Banai et al.
2005
). The antiproliferative effect of nanoencapsulated tyrphostin was found to be
considerably higher than that of surface-adsorbed drug. In the pig model, intramu-
ral delivery of AGL-2043 resulted in reduced in-stent neointima formation in the
coronary arteries as compared to control despite similar degrees of wall injury. The
results of this study suggest that locally delivered tyrphostin AGL-2043 formulated
in biodegradable nanoparticles may be applicable for antirestenotic therapy inde-
pendent of stent design or type of injury.
Controlled Delivery of Nanoparticles to Injured Vasculature
Optimal size of nanoparticles designed for systemic delivery is approximately
50-150 nm, but this size range confers a high surface area-to-volume ratio, which
results in fast diffusive drug release. Spatial control has been achieved by biopan-
ning a phage library to discover materials that target abundant vascular antigens
exposed in disease (Chan et al.
2010
). Temporal control is achieved by designing
60-nm hybrid nanoparticles with a lipid shell interface surrounding a polymer core,
which is loaded with slow-eluting conjugates of paclitaxel for controlled ester
hydrolysis and drug release over approximately 12 days. The nanoparticles inhibit
human aortic smooth muscle cell proliferation in vitro and showed greater in vivo
vascular retention during percutaneous angioplasty as compared to nontargeted
controls. This nanoparticle technology may potentially be used toward the treatment
of injured vasculature.
IGF-1 Delivery by Nanofibers to Improve Cell Therapy
for Myocardial Infarction
Strategies for cardiac repair include injection of cells, but these approaches have
been hampered by poor cell engraftment, survival, and differentiation. To address
these shortcomings for the purpose of improving cardiac function after injury,
a self-assembling peptide nanofibers was designed for prolonged delivery of
insulin-like growth factor 1 (IGF-1), a cardiomyocyte growth and differentiation
factor, to the myocardium, using a “biotin sandwich” approach (Davis et al.
2006
).
Biotinylated IGF-1 was complexed with streptavidin and then bound to biotinylated
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