When one refers to ‘targeted
treatment’ or ‘targeted drug delivery’ the typical assumption is that the treatment
is targeted towards cancer cells. This is, indeed, a very widely used
application of these techniques, however it is not the only one. One of the
primary contributing factors to heart disease is a pathological local inflammatory
response which leads to white-blood-cell invasion of and subsequent thickening/hardening
of arterial walls. Recently this has been sought as a manner to treat heart
disease in addition to conventional therapies such as cholesterol lowering
statins, etc. One manner to treat this is the localized delivery of pro-resolving
peptide mediators such as Ac2-26, which binds to GPCR to effect a powerful
anti-inflammatory response that reduces oxidative stress and plaque necrosis.
Recently, researchers used PLGA-PEG-Maleimide to create a collagen IV targeted
nanoparticle for the localized delivery of Ac2-26 anti-inflammatory peptide to atherosclerotic lesions. Testing in mouse models
showed promise for this method of treatment. PLGA-PEG-Maleimide is one of the
many activated precursor polymers available from PolySciTech Division of Akina,
Inc (www.polyscitech.com). Read more
about the research here: Fredman, Gabrielle, Nazila Kamaly, Stefano Spolitu,
Jaclyn Milton, Devram Ghorpade, Raymond Chiasson, George Kuriakose, Mauro
Perretti, Omid Farokzhad, and Ira Tabas. "Targeted nanoparticles
containing the proresolving peptide Ac2-26 protect against advanced
atherosclerosis in hypercholesterolemic mice." Science translational
medicine 7, no. 275 (2015): 275ra20-275ra20. Fulltext: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397585/
“Abstract: Chronic,
nonresolving inflammation is a critical factor in the clinical progression of
advanced atherosclerotic lesions. In the normal inflammatory response,
resolution is mediated by several agonists, among which is the
glucocorticoid-regulated protein called annexin A1. The proresolving actions of
annexin A1, which are mediated through its receptor N-formyl peptide receptor 2
(FPR2/ALX), can be mimicked by an amino-terminal peptide encompassing amino
acids 2–26 (Ac2-26). Collagen IV (Col IV)–targeted nanoparticles (NPs)
containing Ac2-26 were evaluated for their therapeutic effect on chronic,
advanced atherosclerosis in fat-fed Ldlr−/− mice. When administered to mice
with preexisting lesions, Col IV–Ac2-26 NPs were targeted to lesions and led to
a marked improvement in key advanced plaque properties, including an increase
in the protective collagen layer overlying lesions (which was associated with a
decrease in lesional collagenase activity), suppression of oxidative stress,
and a decrease in plaque necrosis. In mice lacking FPR2/ALX in myeloid cells,
these improvements were not seen. Thus, administration of a resolution-mediating
peptide in a targeted NP activates its receptor on myeloid cells to stabilize
advanced atherosclerotic lesions. These findings support the concept that
defective inflammation resolution plays a role in advanced atherosclerosis, and
suggest a new form of therapy.”
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