Monday, April 4, 2016

PLGA polymers from PolySciTech used in development of localized resolvin D1 delivery for heart-treatment

PolySciTech division of Akina, Inc (www.polyscitech.com) provides a wide array of biodegradable polymers including PLGA. One of the strengths of PolySciTech is providing a fairly comprehensive array of PLGA’s with varying lactide:glycolide ratio as well as molecular weight. These parameters affect biodegradation as higher lactide content and higher molecular weight polymers degrade more slowly.  Recently, researchers at University of California Department of Surgery and Cardiovascular Research Institute used a series of PLGA polymers purchased from PolyScitech to develop a localized drug delivery film which had a gradient of lactide content (LA:GA 50:50, 75:25, 85:15) for controlled release of resolvin D1, a lipid mediator which assist in ending inflammation and assisting healing of the vascular wall. One application of this film would be its potential for use in cardiovascular stents. Currently, these are loaded with cytotoxic anti-proliferative agents which prevent in-healing for a time by simply reducing cell growth. The delivery of a mediator which reduced inflammation and aided healing would bring about a more long-lasting solution to the incidence of in-growth. Read more about this exciting research here: Wu, Bian, Giorgio Mottola, Anuran Chatterjee, Kevin D. Lance, Mian Chen, Iris O. Siguenza, Tejal A. Desai, and Michael S. Conte. "Perivascular delivery of resolvin D1 inhibits neointimal hyperplasia in a rat model of arterial injury." Journal of Vascular Surgery (2016). http://www.sciencedirect.com/science/article/pii/S0741521416001580

“Abstract: Objective: Lipid mediators derived from omega-3 polyunsaturated fatty acids such as resolvin D1 (RvD1) accelerate the resolution of inflammation and have potential as vascular therapeutics. The objective of this study was to evaluate local perivascular delivery of RvD1 as a means to attenuate neointimal hyperplasia in a rat model of arterial injury. Methods: Smooth muscle cells were harvested from rat aortas to study the effects of RvD1 on rat arterial vascular smooth muscle cell responses in vitro, with focus on inflammation, proliferation, migration, cytoskeletal changes, and cytotoxicity. The safety and efficacy of perivascular delivery of RvD1 through thin biodegradable three-layered poly(lactic-co-glycolic acid) wraps or 25% Pluronic F127 gels were studied in a rat model of carotid angioplasty. A total of 200 ng of RvD1 was loaded into each construct for perivascular delivery after injury. Morphometric and histologic analyses were performed 3 and 14 days after injury. Results: RvD1 attenuated rat arterial vascular smooth muscle cell inflammatory pathways, proliferation, migration, and mitogen-induced cytoskeletal changes in vitro, without evidence of cytotoxicity. RvD1-loaded wraps reduced neointimal formation after carotid angioplasty by 59% vs no-wrap controls (P = .001) and by 45% vs vehicle-wrap controls (P = .002). RvD1-loaded Pluronic gels similarly reduced neointimal formation by 49% vs no-gel controls (P = .02) and by 52% vs vehicle-gel controls (P = .02). No group was associated with infection, thrombosis, or negative vessel remodeling. Wraps were found to be easier to apply than gel constructs. Ki67 proliferation index was significantly lower in RvD1-loaded wrap-treated arteries compared with both no-wrap and vehicle-wrap controls at both 3 and 14 days after injury (65% vs no-wrap group and 70% vs vehicle-wrap group at day 3, 49% vs both control groups at day 14; P < .05). Similarly, oxidative stress (30% and 29%; P < .05) and nuclear factor κB activation (42% and 45%; P < .05) were significantly lower in the RvD1-loaded wrap group compared with both no-wrap and vehicle-wrap controls at 3 days after injury. Conclusions: Local perivascular delivery of RvD1 attenuates formation of neointimal hyperplasia without associated toxicity in a rat model of carotid angioplasty. This effect is likely due to attenuation of inflammatory pathways as well as decreased arterial smooth muscle cell proliferation and migration.”
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