Percutaneous transluminal coronary angioplasty (PTCA) is one of the most effective methods of treating atherosclerosis disease, but long-term curative effect is greatly affected by restenosis. Restenosis is a complex process. Mechanism contributing to restenosis include elastic recoil, smooth muscle cell migration and proliferation, enhanced extracellular matrix synthesis, vessel wall remodeling, and thrombus formation. Monocytes/macrophages infiltration and excretion of vasoactive cytokins play an important role during the proceess of restenosis. Monocyte chemotactic protein-1 (MCP-1) is the specific monocyte chemoattractant and has the function of monocytes recruitment. Conventional pharmacological therapy, despite success in animal studies has yet to demonstrate an unambiguous prevention of restenosis in clinical trials. Researchers developed the working hypothesis that the regional nature of restenosis can be best treated with direct local administration of potentially useful compounds Nanoparticles with 30-500 nm in diameter can easily pass through any catheter and vessel wall, and also can be uptake by tissue cells. The agents incorporated into NP can release sustainedly. Using anti-MCP-1 antibodys, corticoid and immunosupressors can reduce intimal hyperplasia in the animal experiments.In our study, biodegradable co-polymer polylactic-polyglycolic acid (PLGA) was used as carrier matrix to formulate nanoparticles containing dexamethasone by emulsification solvent evaporation technique, and then be characterized. NPs and dexamethasone NPs were intraluminally administered in single infusion after balloon injury in the rabbit iliac model. Biocompatibility of NPs and the effects of dexamethasone NPs on prevention of neointimal formation were evaluated. Furthermore, experimental hyperlipidemia carotid injury models were eatablished, the efects of local expression of antisense MCP-1 gene on MCP-1 gene expression and neointimal formation were also evaluated.
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