The Study On PH-responsive Catechol-modified Chitosan/Hyaluronic Acid Drug-loaded Coating

In the world,cardiovascular diseases have the highest morbidity and mortality in all diseases which are higher than tumors and other diseases and pose a great threat to human's health and life.Cardiovascular disease?CVD?is one type of vascular disease which is extremely dangerous.Atherosclerosis is the main cause of coronary heart disease.Percutaneous coronary intervention can restore the normal circulation of blood in the blood vessels,and it's the main method for clinical treatment of atherosclerosis.Vascular stents have been widely used clinically as a necessary medical implant device for percutaneous coronary intervention.Drug-eluting stents as the second generation of vascular stents are currently the most safe and effective stents which are widely used in clinical practice.They consist of bare metal stents,surface polymer coatings and drug loading.However,traditional drug-eluting stents can only passively release drugs with the erosive process of polymer layers,and cannot regulate the rate of drug release.In particular,stents loaded with anti-proliferative drugs may delay the vascular endothelialization due to over-treatment,which may cause late stent restenosis and endanger the patient's health.This topic addresses the low pH environment of the atherosclerotic inflammatory region and aims to construct a pH-responsive films that can regulate drug release.In this study,chitosan and hyaluronic acid with good biocompatibility were selected as the raw materials,and used to assemble layers after modified with catechol structural substances.QCM-D was used to test the stability and pH-responsive of the film.In addition,aspirin was used to synthesize a novel hydrogen sulfide sustained-release aspirin?ACS14?,which can slowly release hydrogen sulfide as an organic donor molecules.Cell culture and cck-8 test were applied to assess the interaction between endothelial cells and hydrogen peroxide including the effect of different concentrations of drugs against endothelial cells,the proliferation of cells and the protection against hydrogen peroxide-induced oxidative stress damage.Finally,the drug was entrapped in the film by physical adsorption and resulting in a novel drug-loaded films that can release the drugs dynamically and varys the dose with the change of environmental pH value and performed a preliminary study of endothelial cell proliferation.Studies on the biological effects of the drug ACS14 have shown that the drug ACS14has the effect of promoting endothelial cell proliferation at low concentrations?1-10?mol/L?,and with the increase of drug concentration,the promotion effect is more obvious.And the drug ACS14 has similar properties as the parent drug aspirin,which can protect endothelial cells from H₂O₂-induced oxidative stress injury.The layer self-assembled thin film with no drug loaded can keep the cell activity well,but the proliferative effect is not obvious.The thin film loaded with 50?mol/L and 100?mol/L drug ACS14 has a good effect on promoting the proliferation of endothelial cells,and the endothelial cells maintain a good morphology and has a higher cell activity.The environment-responsive releasing hydrogen sulfide coating can be applied to the surface of vascular interventional devices stably to have a targeted therapeutic treatment on Diseased blood vessels,thus it can effectively ensure the ensuring the effectiveness and safety of the interventional device applications.