Design, Preparation And Evaluation Of Polymer Coating For Drug-eluting Stents

Ischemic diseases induced by atherosclerosis are severe threats to mankind's health,and percutaneous stem implantation is an important method to deal with vascular stenosis. Because bare metal stems tend to induce acute thrombosis and in-steM restenosis, drug-eluting stents have been developed based on those traditional metal stents.Drug-eluting stents and correlated coating preparation and controlled drug release technology consist of the knowledge in materials,medicine,pharmacy,biology,mechanics and high polymer chemistry, and these stents are real high-technology products.To study the coating design,preparation and evaluation of drug-eluting stents,physical and chemical properties,drug release kinetics and porous surfaces for both non-degradable and degradable coatings are researched in this paper,furthermore,computing software MATLAB and Monte Carlo method are applied for the analysis and optimization of degradation properties and drug release kinetics for degradable system.The paper includes the following content:1.The interaction between sirolimus and drug carrier(acrylate resin or poly (lactic-co-glycolic acid)(PLGA)) was thoroughly researched.Sirolimus is a kind of anti-proliferation drug,and acrylate resin is a kind of universal non-degradable biomaterial, moreover,PLGA is a kind of biodegradable medical polymer.For the blend system of drug and carrier,the results of experiment indicated no chemical reaction happened between them, and the peak intensity is only the sum of two componems.Furthermore,sirolimus had higher solubility in PLGA system than that in acrylic resin system,and the PLGA system also had better thermal stability than acrylic resin system.Pure sirolimus is in a state of polycrystalline powder,while carrier will inhibit the crystallization of sirolimus,and the blends showed no obovious crystal peak.2.316L stainless steel samples were treated uing a kind of silane coupling agent namedγ-aminopropyltriethoxysilane(γ-APS) to active the substrate surface,and this treatment made casting solution spread effectively and enhanced the adherence between coating and substrate. In addition,γ-APS layer can provide early protection of the stainless steel substrate,and avoid adherence decrease due to substrate corrosion.3.The degradation properties of PLGA coatings were simulated and analyzed using Monte Carlo method and the results indicated this method could be used to predict the degradation properties of bulk erosion materials.The degradation and erosion of PLGA could be divided into four stages:Ⅰ—early mass loss stage,Ⅱ—quasi-stable stage,Ⅲ—fast mass loss stage,Ⅳ—breakdown stage,and the accumulation and vanishing of closed and degradated regions controlled the occurring and ending time of stageⅢ.The degradation properties of PLGA coatings could be controlled by operating the transformation of closed and degradated regions and "controlled mass loss" will achieve.4.The degradation properties of blend film and gradient film were analyzed and contrasted with each other.A blend film had balanced degradation property between two original components,and by adjusting the ratio of two components the degradation property of the blend could be easily controlled and "time mass loss" was achieved.A gradient film could be obtained by different ratio of two components in each sublayer,and this non-uniform structure could improve the degradation property of PLGA coating,when PLGA with higher degradation rate such as PLGA50/50 was distributed gradually from outer to inner part of matrix,stable mass loss curve could be obtained.5.The drug release kinetics of acrylic resin and PLGA drug contained coatings were tested and numerically simulated.The release curves of non-degradable acrylic resin coatings almost fit Higuchi's model,while the existence of constant part made the curves deviate the standard Higuchi's model.For the degradable drug contained PLGA system,the drug diffusion coefficient was critically changed due to matrix degradation,and that would complicate the drug release process.The drug diffusion coefficient was considered as the function of distance and time,and calculated using Monte Carlo-diffusion combined model in this paper.The calculating result indicates that the result of above method is better than that of Higuchi's model,and it fit the experiment data well.To contrast the acrylic resin and PLGA,sirolimus tends to diffuse faster in PLGA systerm under the same condition.6.Polyurethane(PU) and PLGA porous coatings by phase inversion method were obtained on the surface of 316L stainless steel,and the pore diameter was controlled by alternating casting solution concentration and atmospheric humidity.It was observed that pore diameter increased with the increase of casting solution concentration and the decrease of atmospheric humidity.PU casting solution tended to form pore-in-pore structure under under the condition of low solution concentration and high atmospheric humidity,and the probability of this phenomenon could be effectively decreased by increasing solution concentration.For PLGA coatings,island structure appeared under the condition of low atmospheric humidity due to the worse ability of pore formation than PU.The contact angle experiment showed strong hydrophobicity of porous coatings,and platelet adhesion experiment indicated that strong hydrophobicity resulted in the decrease of binding energy between platelets and coating surfaces.The surfaces of porous coatings had the least amount of platelets,and there was no significant change on the morphology of platelets.All of above factors make PU porous coatings achieve excellent blood compatibility.