Biomedical Engineering Reference
In-Depth Information
might be necessary to treat the multifactorial nature of pathological thrombogenesis.
For this purpose, a nanoscale device that can carry such a combination selectively
to a thrombotic site is being developed at the Department of Biomedical Engineering
of Case Western Reserve University (Cleveland, OH). The liposomal nanodevice
surface is modified by RGD (Arginine-Glycine-Aspartic Acid) motifs that specifi-
cally targets and binds activated platelets by virtue of the high affinity interaction
between the RGD-motif and the integrin GPIIb-IIIa expressed on active platelets,
potentially acting as a thrombus-targeted vector. The ability of such liposomes to
compete with native ligand fibrinogen in specifically binding activated platelets has
been accomplished using both in vitro and in vivo approaches. The results demon-
strate feasibility of using liposomes as platelet-targeted devices for delivery of
cardiovascular therapeutics. By utilizing a library of synthetic peptide/peptidomi-
metic ligands having binding affinity toward specific receptors expressed in cardio-
vascular biology, it is possible to manipulate the liposome surface-modification and
hence dictate targeting specificity and affinity of the liposomal nanodevices.
Low Molecular Weight Heparin-Loaded Polymeric Nanoparticles
Low molecular weight heparin (LMWH) nanoparticles are available as potential
oral heparin carriers. The nanoparticles are formulated using an ultrasound probe
by water-in-oil-in-water emulsification and solvent evaporation with polymers. The
mean diameter of LMWH-loaded nanoparticles ranges from 240 to 490 nm and is
dependent on the reduced viscosity of the polymeric organic solution. The highest
encapsulation efficiencies are observed when Eudragit polymers are used in the
composition of the polymeric matrix. The in vitro biological activity of released
LMWH, determined by the anti-factor Xa activity with a chromogenic substrate, is
preserved after the encapsulation process, making these nanoparticles good candi-
dates for oral administration.
Nanoparticles for Cardiovascular Imaging
and Targeted Drug Delivery
The potential dual use of nanoparticles for both imaging and site-targeted delivery
of therapeutic agents to cardiovascular disease offers great promise for individual-
izing therapeutics. Image-based therapeutics with site-selective agents should enable
verification that the drug is reaching the intended target and a molecular effect is
occurring. Experimental studies have shown that binding of paclitaxel to smooth
muscle cells in culture has no effect in altering the growth characteristics of the cells.
If paclitaxel-loaded nanoparticles are applied to the cells, however, specific binding
elicits a substantial reduction in smooth muscle cell proliferation, indicating that
selective targeting may be a requirement for effective drug delivery in this situation.
Similar behavior has been demonstrated for doxorubicin-containing particles.
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