Drug Release Properties And Optimization Design Of Degradable Drug-eluting Stent

The degradation behavior of degradable polymer drug-loaded coating directly affects the sustained release process of the drug in the blood vessel.Therefore,it is of great guiding significance to study the degradation behavior of the degradable coating material,the mechanism of drug release in the degradation process,and the optimal design of the drug sustained release process in the degradation process for improving the drug release effect of the drug-eluting stent.In this paper,the degradation behavior of the stent coating material polylactic acid(PLA)was studied in a human-like liquid environment,and the changes of quality,surface micromorphology,mechanical strength,molecular weight and distribution of polylactic acid in the degradation process were obtained;Secondly,the finite element method was used to study the drug release process of drug-eluting stent in vascular wall,the influence of coating parameters on the drug sustained-release process was analyzed,and the key factors affecting the drug sustained-release effect were obtained;Finally,an improved optimization design method based on Kriging surrogate model was used to optimize the key parameters of the coating to achieve the purpose of improving the effective drug release time of drug-eluting stent.The main contributions of the thesis can be summarized as follows:(1)The degradable polymer coating material polylactic acid was used as the research object for a one-year in vitro degradation experiment.The experimental results show that with the increase of degradation time,there are white degradation products precipitated on the surface of PLA specimens,accompanied by specimen bending,swelling and rupture.The surface and section of the specimen will produce small holes.The mechanical properties of the specimens decrease with the deepening of degradation.After 50 weeks of degradation,the tensile strength and elastic modulus of the specimens decrease by 91.90% and 73.14%,respectively.The molecular weight of PLA specimens decreases from fast to slow.At the 50 th week of degradation,the weight-average molecular weight of the specimens is decreased by 84.1%,which has a great influence on the mechanical properties of polylactic acid specimens.(2)A complete mathematical model was established for drug release process of drug-eluting stent.The finite element method was used to simulate the coupling problem between the velocity field and the concentration field involved in the drug sustained-release process.The drug sustained-release process of biodegradable drug-eluting stent was studied,and the distribution and change of the drug in vascular wall during the degradation process were obtained.The results show that there are eddy currents on both sides of the stent rib,which causes the drug not easy to be eluted by blood flow;The initial drug concentration of the coating has a great influence on the peak value of the drug concentration in the vascular wall,while the coating thickness and the degradation rate coefficient of the coating have a great influence on the drug release time in the vascular wall,and the distribution of the drug concentration in the vascular wall is obtained,which reveals the drug release law of drug-eluting stent with degradable coating.(3)Based on the simulation and analysis of drug release process of drug-eluting stent,Kriging surrogate model optimization algorithm combined with finite element method was proposed to optimize the degradable polymer coating of drug-eluting stent.The coating thickness,the initial drug concentration and degradation rate of coating were used as design variables,and the effective drug release time of stent during the drug release process was used as the optimization objective.The optimization results show that the effective time of the drug after optimization is 8499300 s,and the effective time of the drug obtained by the optimal parameters in the initial sample point is 3796500 s.The effective drug release time in the vascular wall is greatly prolonged,which is beneficial to reduce the risk of in-stent restenosis.And it is shown that the Kriging surrogate model optimization method can be effectively applied to the optimal design of drug-loaded coatings for degradable drug-eluting stents.