The Research Of Atorvastatin Calcium/EGCG Dual Eluting Coating

Atherosclerotic Cardiovascular disease has become one of the major diseases that threaten human health.Drug-eluting stents(DES)are generally used as the first choice of coronary stents in the field of interventional cardiology.Coronary artery stents significantly reduce the risk of restenosis and the need for revascularization but there are still some problems.A recent pathological study indicated that the polymers were still exist in the long term in vivo after the drug completely released,which may result in inflammation,delay of endothelialization,cause late thrombosis,inhibit neoatherosclerosis and other complications.Some drugs including rapamycin,paclitaxel and derivatives coated onto stents inhibit vascular smooth muscle cell proliferation and also inhibit endothelial cells proliferation,which this indiscriminating inhibition may delay endothelial repair.A dysfunctional endothelium favors prothrombotic surface as well as the development of neoatherosclerosis within the stented segment,owing to accelerated lipid uptake and inflammatory cell migration.Facing the above problems,one strategy is to adopt biodegradable polymers as drug carrier and choose drugs with specific action.Polytrimethylene carbonate(PTMC)as one kind of surface erodible polymer,which has good biocompatibility and mechanical properties and has been approved by FDA,can be used as a stent coating material.Two kinds of drugs atorvastatin and epigallocatechin-3-gallate(EGCG)were combined as has the effect of protecting vascular intima,increasing atherosclerotic plaque stability,anti-inflammatory,and anticoagulation.Epigallocatechin-3-gallate(EGCG)is one of antioxidants,which could inhibit smooth muscle cell proliferation.Construct a drug coating which have anticoagulant,inhibition of smooth muscle proliferation,promote endothelial repair and other functions.In this paper,PTMC as the carrierand atorvastatin calcium/EGCG(molar ratio 1:1)dual eluting coating was prepared.The results of backwashing and Fourier transform infrared spectroscopy(FTIR)proved that atorvastatin calcium/EGCG coating had been successfully prepared.From the observation of optical microscopy and scanning electron microscopy(SEM),it could be found that there was no obvious drug enrichment on the coating surface,and the drug distribution was uniform.The measurement of water contact angle indicated that the hydrophilicity of the drug-coated coating is improved compared to 316L stainless steel.In vitro release study showed that the atorvastatin calcium/EGCG coating had a good drug-controlled release which could steadily and continuously release the drug.In vitro platelet adhesion and activation experiments indicateded that atorvastatin calcium/EGCG coating significantly inhibited platelet adhesion and activation.The measurement of NO total amount of endothelial cell culture medium showed that the atorvastatin calcium/EGCG coating could promote the release of NO.When the concentration of atorvastatin calcium was higher than 2umol/L,it showed endothelial cytotoxicity,but when he concentration of atorvastatin calcium was lower than 2umol/L,it could promote endothelial cell proliferation.The atorvastatin calcium/EGCG coating exhibited inhibiting the growth of smooth muscle cells as well as promoting the proliferation of endothelial cells.In vitro macrophage and inflammatory factors evaluation showed that the atorvastatin calcium/EGCG coating can inhibit macrophage proliferation.The endothelial progenitor cell chemotaxis chamber experiments indicated that the atorvastatin calcium/EGCG eluting coating can promote the migration of endothelial progenitor cells.In order to accurately evaluate the function of the atorvastatin calcium/EGCG eluting coating in the artery,the double drug coating and rapamycin coating wwere respectively prepared on a diameter of 100 μm stainless steel wire by ultrasonic atomization spray.Then the samples were implanted in the abdominal aorta of SD rats for 3 weeks.The results of the sample removal after 3 weeks showed that the atorvastatin calcium/EGCG coating sample had more complete endothelialization than the rapamycin coating and the stainless steel sample.HE and immunofluorescence staining test indicated that the atorvastatin calcium/EGCG coating could reduce intimal hyperplasia and had a complete endothelialium in the outer layer of blood contact surface,and the smooth muscle cells were arranged between the sample and the endothelium.These results suggested that the atorvastatin calcium/EGCG dual eluting coating can be improved endothelialization.This study proves that the atorvastatin calcium/EGCG dual eluting coating have the effect of reducing vascular endothelial dysfunction and good blood compatibility.The atorvastatin calcium/EGCG dual eluting coating is the potential candidate to be used in novel DES.