PLA-Fluorescein from PolySciTech used in PhD thesis work on development of theranostic nanoparticles for treatment of heart-disease
A critical yet often overlooked factor in atherosclerosis
(heart-disease) is inflammation, as swelling contributes to the constriction of
the blood vessels and damage to the tissue. This also presents a potential
therapeutic target as preventing inflammation can assist with reducing the
incidence of morbidity and mortality with this disease. Recently, researchers
at Massachusetts Institute of Technology used P(DL)La and P(DL)La-Fluorescein
(PolyVivo AV016) from PolySciTech (www.polyscitech.com)
to develop nanoparticles to deliver simvastatin to affected tissue. The use of
fluorescein conjugated PLA allowed for easy tracking of the nanoparticles by visual
techniques. This research holds promise to treat inflammatory diseases. Read
more: Chung, Bomy Lee. "Theranostic nanoparticles for the management of
inflammatory diseases and conditions." PhD diss., Massachusetts Institute
of Technology, 2017. https://dspace.mit.edu/handle/1721.1/112504
“Abstract: Atherosclerosis,
the gradual buildup of plaques within arteries, is the main cause of
cardiovascular diseases (CVDs). The World Health Organization reports that CVDs
are the number one cause of death in the world. In the United States alone,
around 85 million people suffer from CVDs; this is associated with a cost of
over $316 billion per year and responsible for about a third of all deaths in
the US. Recent findings have shown that inflammation plays a pivotal role in
atherosclerosis. Although statins have traditionally been prescribed for their
lipid-lowering benefits, studies have indicated that they can have other
effects as well (so-called "pleiotropic effects"), including
anti-inflammatory, anti-oxidant, and anti-thrombotic benefits. This thesis presents
a novel theranostic (therapeutic + diagnostic) nanoparticle platform for the
treatment and diagnosis of atherosclerosis. Given the anti-inflammatory effects
of statins when cells are directly treated, the aim of this nanoparticle
platform was to target macrophages within plaques given their central role in
plaque development and progression. First, simvastatin-loaded nanoparticles
were designed and optimized. The particles consisted of a biodegradable polymer
core and a lipid shell. Using bulk nanoprecipitation methods, as well as
microfluidic devices, the physical characteristics of the particles could be
controlled and fine-tuned to meet the desired specifications: 100 to 200 nm in
size, -15 to -20 mV in zeta potential, and 70%+ simvastatin loading efficiency.
Imaging agents, such as iron oxide nanocrystals used for magnetic resonance
imaging (MRI), were successfully incorporated into the nanoparticles and can offer
diagnostic capabilities to the nanoparticles. Next, various nanoparticle
formulations were shown to be therapeutically effective in cell and mice models
of atherosclerosis. For instance, in vitro treatment of macrophages led to
decreases in the expression of TNF-a and MCP-1 by roughly 20% and 50%,
respectively. This pattern has also been observed in murine models, with
researchers showing that simvastatin-loaded particles can halt plaque
development (and even decrease plaque area) while reducing the expression of
pro-inflammatory genes (e.g., of TNF-a, IL- IP) by an order of magnitude.
Overall, this thesis presents a new and innovative nanoparticle platform that
has the potential for the simultaneous treatment and diagnosis of
atherosclerosis. Given their anti-inflammatory benefits, these nanoparticles
have the potential to impact the treatment of not only atherosclerosis but also
various other inflammatory conditions and diseases as well.”
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