Tuesday, December 1, 2015

PLGA-PEG-Maleimide used for targeted treatment of heart disease

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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