Biomedical Engineering Reference
In-Depth Information
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Manufacture of nanoparticle formulations with controlled particle sizes,
morphology, and surface properties would be more effective and less expensive
than other technologies.
Nanoparticle formulations that can provide sustained release profiles up to 24 h
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can improve patient compliance with drug regimens.
Direct coupling of drugs to targeting ligand restricts the coupling capacity to a
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few drug molecules but coupling of drug carrier nanosystems to ligands allows
import of thousands of drug molecules by means of one receptor targeted ligand.
Nanosystems offer opportunities to achieve drug targeting with newly discov-
ered disease-specific targets.
The future of cardiovascular diagnosis already is being impacted by nanosys-
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tems that can both diagnose pathology and treat it with targeted delivery
systems.
Controlled delivery of nanoparticles to injured vasculature.
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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.
Intravenous delivery of fumagillin (an antiangiogenic agent)-loaded nano-particles
targeted to avb3-integrin epitopes on vasa vasorum in growing plaques results in
marked inhibition of plaque angiogenesis in cholesterol fed rabbits. The unique
mechanism of drug delivery for highly lipophilic agents such as paclitaxel contained
within emulsions depends on close apposition between the nanoparticle carrier and
the targeted cell membrane and has been described as “contact facilitated drug deliv-
ery.” In contrast to liposomal drug delivery (generally requiring endocytosis), the
mechanism of drug transport in this case involves lipid exchange or lipid mixing
between the emulsion vesicle and the targeted cell membrane, which depends on the
extent and frequency of contact between two lipidic surfaces. The rate of lipid
exchange and drug delivery can be greatly increased by the application of clinically
safe levels of ultrasound energy that increase the propensity for fusion or enhanced
contact between the nanoparticles and the targeted cell membrane.
The combination of targeted drug delivery and molecular imaging with MRI has
the potential to enable serial characterization of the molecular epitope expression
based on imaging readouts. Monitoring and confirmation of therapeutic efficacy of
the therapeutic agents at the targeted site would facilitate personalized medical
regimens.
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