Prednisolone- and sirolimus-eluting stent: Anti-inflammatory approach for inhibiting in-stent restenosis

Abstract

Glucocorticoids are powerful anti-inflammatory, immunosuppressive, and anti-proliferative agents. The aim of this study was to evaluate the effectiveness of a prednisolone- (PDScs) and sirolimus-coated stent (SRLcs) in preventing artery vessel neointimal hyperplasia and inflammatory reactions in vitro and in vivo. PDS, a synthetic glucocorticoid, is a derivative of cortisol, which is used to treat a variety of inflammatory and autoimmune conditions. The stents were fabricated with PDS, SRL, or both agents using a layer-by-layer coating system (designated as PDScs, SRLcs, and PDSRLcs, respectively). The surface morphology of the PDScs showed an evenly dispersed and roughened shape, which was smoothened by the SRL coating. Half of the total drug amounts were released within seven days, followed by an additional release, which continued for up to 28 days. The proliferation of smooth muscle cells was inhibited in the SRLcs group (31.5 ± 4.08%), and this effect was enhanced by PDS addition (PDSRLcs, 46.8 ± 8.11%). Consistently, in the animal study, the restenosis rate was inhibited by the SRLcs and PDSRLcs (18.5 ± 6.23% and 14.5 ± 3.55%, respectively). Especially, fibrin expression and inflammation were suppressed in the PDS-containing group (PDScs, 0.6 ± 0.12 and 1.4 ± 0.33; PDSRLcs, 0.7 ± 0.48 and 1.7 ± 0.12, respectively) compared to PDS non-containing groups (BMS, 1.1 ± 0.12, and 1.8 ± 0.55; SRLcs, 1.6 ± 0.32 and 2.0 ± 0.62, respectively). Moreover, re-endothelialization was enhanced in the PDScs group as determined using immunohistochemistry with a cluster of differentiation (CD)-31 antibodies. These results suggest that the inhibitory effect of SRLcs on anti-restenosis can be accelerated by additional coating with PDS, which has promising properties as a bioactive compound with useful anti-inflammatory effects.