An advanced antisense for local and stent based delivery for prevention of restenosis

In-stent restenosis remains an unresolved problem, which occurs in 10-50% of patients undergoing coronary stenting within the first 3-6 months.1,2 Neointimal formation is the main contributor to in-stent restenosis.3,4 Stentinduced arterial injury and peristrut inflammation are involved in the process of neointimal formation by activating cytokines and growth factors, which induce smooth muscle cell dedifferentiation, migration, and proliferation.5,6 Histopathological studies found that neointimal hyperplasia is principally composed of smooth muscle cells, inflammatory cells, and extracellular matrix.7,8 Stentbased delivery of antiproliferative and/or antiinflammatory agents have shown beneficial effects on neointimal hyperplasia in experimental studies and clinical trials.9,10Tacrolimus (FK506) is a water-insolublep macrolide immunosuppressant which was discovered in 1984.11 It has been widely used in reducing the incidence and severity of allograft rejection after organ transplantation.12 It has also been used to treat other inflammatory conditions, such as atopic dermatitis.13,14 In this study, we evaluated the efficacy of stent-based delivery of tacrolimus on inflammation and neointimal formation in an over-stretched coronary stent model.