基于聚异丁烯的嵌段共聚物的合成、表征及在生物医用材料中的应用

发布时间：2018-03-14 20:11

本文选题：聚合物前药　切入点：生物可降解性　出处：《苏州大学》2015年硕士论文　论文类型：学位论文

【摘要】：聚异丁烯(PIB)是一种具有粘性的高分子聚合物,有很好的抗热、抗紫外线和抗氧化的性能。利用这些特性,可以制作新型的热塑性弹性体、自愈合材料等。同时,PIB是一种具有良好生物相容性的柔性高分子聚合物。据文献报道,聚异丁烯与一些常见聚合物共聚,能形成具有良好生物相容性、良好非发炎性的潜在生物材料。本论文主要研究基于聚异丁烯的嵌段共聚物的合成、表征,以及在药物洗脱支架涂层材料和水凝胶敷料中的应用。第一部分聚合物前药Paclitaxel-Poly(lactic acid)-b-Polyisobutylene的合成、表征及在药物洗脱支架涂层中的应用我们制备了一种用紫杉醇修饰的生物相容性前药PTX-PLA-b-PIB,用于药物洗脱支架涂层材料,可以防止晚期再狭窄。同时,作为对照,我们也制备了两嵌段共聚物PIB-b-PLA作为高分子载体,包载紫杉醇,用作药物洗脱支架涂层。通过核磁共振氢谱(1H NMR)、红外光谱(FT-IR)以及凝胶渗透色谱(GPC)对聚合物的结构、分子量以及分子量分布进行表征。通过水滴接触角、热重分析(TGA)和差示扫描量热法(DSC)对聚合物的疏水性以及热性能进行了分析。涂层的表面结构对支架在体内的释放具有重要影响,通过原子力显微镜(AFM)和扫描电镜(SEM)对涂层和支架的表面结构进行了测试,结果表明,物理包载涂层(PIB-b-PLA/PTX)和前药涂层(PTX-PLA-b-PIB)具有完全不同的表面结构。考察三个体系的药物洗脱支架涂层的体外释放,即前药体系PTX-PLA-b-PIB、聚合物载药体系PIB-b-PLA/PTX以及二者的混合体系,结果表明,混合体系能够使药物洗脱支架(DES)维持稳定的释放,并且能够减小涂层的细胞毒性。由于聚合物的降解对DES的体外释放具有非常重要的影响,我们还进行了涂层的降解实验。第二部分具有酸敏感特性的两亲性嵌段共聚物mPEG-a-PIB的合成、表征及用于构筑水凝胶敷料本文通过“点击化学”反应成功制备了一种带有酸敏感基团的两亲性嵌段共聚物,即聚乙二醇单甲醚-acetal-聚异丁烯(简写为mPEG-a-PIB)。通过1H NMR、FT-IR和GPC对聚合物的结构、分子量及其分子量分布进行表征。通过芘荧光探针法、动态激光光散射(DLS)以及透射电子显微镜(TEM)对聚合物在水相形成胶束的临界聚集浓度、粒径参数以及胶束形态进行了研究。利用DLS对聚合物在酸性条件下粒径的变化进行跟踪测试,研究聚合物的酸敏感特性。在体系中引入α-环糊精(α-CD),诱导形成水凝胶。利用X射线衍射(XRD)分析水凝胶的包结络合作用,并利用流变仪测试水凝胶的黏弹性及凝胶化时间。通过体外细胞毒性测试(MTT)证明聚合物及其所形成的水凝胶具有良好的生物相容性。这种水凝胶能够保持创面湿润,具有温和的冷却作用,并且由于其带有酸敏感基团,具有pH敏感性,能够在偏酸性环境下降解释放出药物,加快创面愈合过程,在水凝胶敷料中具有应用价值。
[Abstract]:Polyisobutene (PIBB) is a kind of viscous polymer with excellent heat resistance, ultraviolet resistance and oxidation resistance, which can be used to make new thermoplastic elastomers. PIB is a kind of flexible polymer with good biocompatibility. According to the literature, polyisobutene copolymerized with some common polymers, which can form good biocompatibility. In this paper, the synthesis and characterization of block copolymers based on polyisobutylene were studied. And applications in drug-eluting stent coating materials and hydrogel dressings. Part I Synthesis of polymer prodrug Paclitaxel-Poly(lactic acid)-b-Polyisobutylene, Characterization and application in drug-eluting stent coating we have prepared a biocompatible prodrug PTX-PLA-b-PIBA modified with paclitaxel to prevent late restenosis. We also prepared diblock copolymers PIB-b-PLA as polymer carrier, encapsulated paclitaxel, as drug eluting stent coating. The structure of the polymer was studied by 1H NMR, FT-IR and GPC-gel permeation chromatography. The molecular weight and molecular weight distribution are characterized by the contact angle of water droplets, Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) were used to analyze the hydrophobicity and thermal properties of the polymer. The surface structure of the coating and the scaffold was measured by AFM and SEM. The results showed that the surface structure of the coating and the scaffold were determined by atomic force microscopy (AFM) and scanning electron microscope (SEM). The PIB-b-PLA-b-PIBX and the prodrug coating PTX-PLA-b-PIB) have completely different surface structures. The in vitro release of the three drug-eluting stent coatings, namely, the prodrug system PTX-PLA-b-PIB, the polymer-loaded drug system PIB-b-PLA/PTX and the mixture of the two systems, were investigated. The mixed system can maintain the stable release of drug-eluting stents and reduce the cytotoxicity of the coatings. The degradation of polymers has a very important effect on the release of DES in vitro. The second part is the synthesis of amphiphilic block copolymer (mPEG-a-PIB) with acid-sensitive properties. Amphiphilic block copolymers with acid-sensitive groups were successfully prepared by "click-chemical" reaction. Poly (ethylene glycol monomethyl ether) -acetal-polyisobutylene (mPEG-a-PIBN). The structure, molecular weight and molecular weight distribution of the polymer were characterized by 1H NMR-FT-IR and GPC. Dynamic laser light scattering (DLS) and transmission electron microscopy (TEM) are the critical concentration of polymer micelles in aqueous phase. The particle size parameters and micelle morphology were studied. The change of polymer particle size under acidic conditions was measured by DLS. The acid-sensitive properties of polymers were studied. 伪 -cyclodextrin (伪 -CDD) was introduced into the system to induce hydrogels to form hydrogels. The inclusion complexation of hydrogels was analyzed by X-ray diffraction (XRD). The viscoelasticity and gelation time of hydrogel were measured by rheometer. MTT showed that the polymer and its hydrogel had good biocompatibility. The hydrogel could keep the wound moist. It has mild cooling effect, and it has acid-sensitive group and pH sensitivity, so it can degrade and release drugs under the condition of partial acid, accelerate wound healing process, and have application value in hydrogel dressing.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：TQ317;R318.08

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