Monday, August 15, 2016

Two types of PLGA from PolySciTech used in development of directional Resolvin delivery-system for improved cardiac care

PolySciTech Division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable polymers for several applications. One of these is PLGA type polymers including a wide array of molecular weights and lactide:glycolide ratios. For this type of polymer, the degradation time increases as the lactide content increases. This allows different types of PLGA to be combined in specific orientations so as to encourage degradation or drug release to preferentially occur on one side. Recently, two PLGA polymers from PolySciTech with different lactide contents (AP061 (LA:GA 75:25 (Mn 35-45 kDa)) and AP021 (85:15 (Mn 35-45 kDa))) were utilized by researchers at UCSF to design a system which delivers Resolvin D1, a mediator which promotes injury recovery, in a directional manner from a thin film with 98% of the resolvin released through the low-lactide side over the course of 56 days. Such a system holds promise for use in cardiac therapy to prevent restenosis of arteries following stenting or other procedures. Read more: Lance, Kevin D., Anuran Chatterjee, Bian Wu, Giorgio Mottola, Harald Nuhn, Phin Peng Lee, Brian E. Sansbury, Matthew Spite, Tejal A. Desai, and Michael S. Conte. "Unidirectional and Sustained Delivery of the ProResolving Lipid Mediator Resolvin D1 from a Biodegradable Thin Film Device." Journal of Biomedical Materials Research Part A (2016). http://onlinelibrary.wiley.com/doi/10.1002/jbm.a.35861/full

“Abstract: Resolvin D1 (RvD1) belongs to a family of endogenously derived pro-resolving lipid mediators that have been shown to attenuate inflammation, activate pro-resolution signaling and promote homeostasis and recovery from tissue injury. In this study we present a poly(lactic-co-glycolic acid) (PLGA) based thin-film device composed of layers of varying ratios of lactic and glycolic acid that elutes RvD1 unidirectionally to target tissues. The device demonstrated sustained release in vitro for 56 days with an initial burst of release over 14 days. The asymmetric design of the device released 98% of RvD1 through the layer with the lowest molar ratio of lactic acid to glycolic acid, and the remainder through the opposite side. We validated structural integrity of RvD1 released from the device by mass spectrometry and investigated its bioactivity on human vascular endothelial (EC) and smooth muscle cells (VSMC). RvD1 released from the device attenuated VSMC migration, proliferation and TNF-α induced NF-κB activation, without evidence of cytotoxicity. Delivery of RvD1 to blood vessels was demonstrated ex vivo in a flow chamber system using perfused rabbit aortas and in vivo in a rat carotid artery model, with the devices applied as an adventitial wrap. Our results demonstrate a novel approach for sustained, local delivery of Resolvin D1 to vascular tissue at therapeutically relevant levels. Keywords: PLGA; resolvin; inflammation; vascular delivery; wrap”
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