Study On Coating Degradation And Drug Release Properties Of Coronary Stent Based On Plla

The fully biodegradable drug-eluting stent is of great significance to the treatment of cardiovascular stenosis and improving the quality of life of patients because of its core advantages that it can selfdegrade and the product is absorbed by the body after it completes support and restores blood flow.The fully degradable drug-eluting stent is composed of the struct and the drug-loaded coating.The struct determines the radial support performance of the stent.The drug-loaded coating is the key to inhibiting thrombosis,inflammation and intravascular restenosis,which becomes the core problem to be solved urgently for the stent.Based on the fully degradable PLLA eluting stent,this thesis studies the degradation and release performance of the drug-loaded coating.The thesis has achieved the following innovative research results:(1)The degradation process model of PDLLA films was established based on the ester bond breakage and short-chain diffusion principle,and the degradation performance of PDLLA films was studied through experiment and simulation,and the numerically average molecular weight degradation curve was obtained.Based on the ester bond breakage and short-chain diffusibility principle,the governing equations for chain scission,the short-chain diffusion equation and the number average molecular weight degradation equation were established.The PLLA isomer-racemic polylactic acid PDLLA film was prepared by casting method,and its degradation in neutral PBS solution at 37 ℃was studied.The experimental results showed that the various indicators of the film changed little in the early stage,and decreased rapidly in the later stage,which was typical of bulk erosion degradation.Comsol Multiphysics,the multiphysics field simulation software,was used to model and calculate the degradation of the film,and the molecular weight simulation curve that was highly consistent with the experimental data was obtained.Then the stability of the numerical solution of the model was evaluated.The bulk degradation mechanism of the material was verified by analyzing the cross-sectional nephogram of the film.After that,the two degradation rate parameters in the model were compared to obtain the degradation curves with different degrees of autocatalytic effect,which were applied to the extension model.(2)The standard curve of drug concentration released in vitro was established,the release medium solution was selected,and the key factors affecting the release rate of drug loaded coating of PDLLA were studied through experiments.It was found that the release mechanism of drug loaded coating was mainly diffusion release.According to the properties of sirolimus,the in vitro drug release study was carried out by high performance liquid chromatography(HPLC).By setting test conditions,establishing the standard curve of drug concentration and optimizing the release medium,the in vitro release medium was finally determined to be 0.1% Brij58/PBS solution.The PDLLA drug-loaded coating samples were prepared by ultrasonic atomization process,and the mechanical properties and adhesion properties of the coating were evaluated.Later,the effects of different factors(drug loading ratio,blank top layer thickness,and hydrophilic polymer PEG)on the release rate of PDLLA drug-loaded coating was studied.The results showed that high polymer ratio would limit the drug release,and thickness and PEG could regulate the initial release of the coating.Korsmeyer-Peppas empirical model was used to fit the release data of each formula,and the fitting parameters n were all less than 0.45.The release mechanism of drug-loaded coating was mainly diffusion release.(3)Based on the ultrasonic atomizing spraying equipment with integrated special clamping module,the blended films with different blending proportions were prepared,the regulating effect of different blending proportions on the release of drug-loaded films was studied,and the release curve was optimized by the convolution method.Combined with the existing ultrasonic atomization spraying equipment,the XY two-dimensional motion platform system was designed and developed to prepare thin film samples.Four blend films of PDLLA and poly(L-lactide-caprolactone)(8020,7030,6040,5050)were sprayed by solvent blending method to study the effect of different blend ratios on the release of drug-loaded films.The overall and segmented fitting of the release curves was performed using the Korsmeyer-Peppas and Higuchi empirical models to analyze the release mechanism,and the release curves were optimized by the convolution method.In this method,the attenuation phenomenon of sirolimus in aqueous solution was considered.The attenuation equation was obtained through recovery testing.Combined with the release data,the theoretical release curves before attenuation were obtained by convolution calculation,so as to realize the optimization of release curve.The convolution method compared the fitting and prediction results of the Weibull equation and the KP equation,which were both in good agreement with the reversed experimental data,and the later prediction of Weibull was relatively more accurate.(4)Based on the microscopic process of polymer degradation and drug release,the dissolutiondegradation-diffusion equations and degradation-diffusion-convection equations of drug-loaded polymer were derived.Combined with the two equations,numerical simulation models of in vitro blend film release and in vivo stent coating release were established respectively,and the accuracy and applicability of the models were verified by experiments.For the in vitro release model,the release profiles of the blended drug-loaded films(6040d,5050d)within 90 days were studied based on the inverted experimental data and Weibull optimization curve.The concentration distribution in the film section was analyzed,and the accuracy and applicability of the model were verified.The mechanism model combined with simulation could better simulate the drug release of the blended film.According to the early-stage anastomotic data,the later release of the film could be predicted,reducing time and experimental cost.For the in vivo release model,the local drug distribution in blood vessels was studied based on the in vitro model,and the drug concentration in the tissue was compared with the clinical data in the literature.The simulation results in vivo and in vitro showed that drug release was greatly affected by the degradation rate of the carrier,and the release rate of the coating was faster in the early-stage,leading to a relatively high boundary concentration at the contact position between the stent and blood vessel.In view of the clinical requirements,it was necessary to add the blank layer on the stent coating,and it was also necessary to select polymer carriers with different degradation rates according to the requirements of controlled release.