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J Nanopart Res (2013) 15:1962 DOI 10.1007/s11051-013-1962-1
RESEARCH PAPER
Advanced stent coating for drug delivery and in vivo biocompatibility
Yi Liu Wuchen Wang Gayathri Acharya
Yoon-Bo Shim Eun Sang Choe Chi H. Lee
Received: 24 January 2013 / Accepted: 20 August 2013 / Published online: 15 September 2013 Springer Science+Business Media Dordrecht 2013
Abstract As an effort to alleviate stent-induced cardiovascular injury including restenosis and thrombosis, advanced drug-eluting stent (ADES) with a bilayer construct composed of a top-coat made of collagen and a base-coat incorporated with N-nitrosomelatonin (NOMela)-loaded PLGA nanoparticles has been developed. NOMela is a hydrophobic prodrug of nitric oxide (NO) that is an endogenous anti-platelet compound. ADES was coated with PLGA nanoparticles via either electrophoretic deposition (EPD) technique or dip-coating technique, and their coating characteristics and efcacies were compared. The drug-loading efcacy and in vitro drug-release proles from ADES were expressed with various variables including the additives to the collagen layer, the number of layers of the collagen top-coat, the hydrophobicity/hydrophilicity of the loaded drug, the coating technique of nanoparticles, and the concentration of coating emulsions in the EPD method. The
morphological status of cross-section and surface of ADES was evaluated by laser scanning confocal microscope and scanning electronic microscope. The real-time release proles of NO were assessed using the NO-microbiosensor. The anti-platelet activity of ADES was evaluated on the rabbit whole blood using an aggregometer. The intima formation and protein expression in aorta were examined using an in vivo rat model. Both collagen and PLGA used in ADES are biodegradable polymers that fully degrade and consequently produce less inammation responses. NO released from ADES signicantly reduced platelet aggregation in the rabbit blood as compared with those exposed to the control stents. ADES coated with a double layer consisted of collagen and PLGA and containing NOMela was less antigenic at the implanted sites and alleviating intima formation and thrombosis. An external exposure of aorta to NO elicits distinct and specic effects on mitogen-activated protein kinase (MAPK) and Ca2?/calmodulin-dependent protein kinase II (CaMKII) activities which evoke the endoplasmic reticulum (ER) stress response. These ndings elucidated that coordinate and reciprocal alterations in the protein kinases followed by the ER stress protein expression are an integral feature of the in-stent-mediated cardiovascular injury.
Keywords Drug-eluting stent Restenosis