壳聚糖基温敏原位凝胶的制备及性能研究

发布时间：2018-05-16 06:08

本文选题：巯基化壳聚糖 + β-甘油磷酸钠　；参考：《天津大学》2012年硕士论文

【摘要】：壳聚糖基水凝胶在药物缓控释和组织工程领域具有很好的应用前景，为了改善壳聚糖基水凝胶的应用性能和生物相容性，本文制备了巯基化壳聚糖，并采用了物理和化学双重交联网络制备了巯基化壳聚糖/β-甘油磷酸钠（CTG）凝胶，研究了CTG凝胶的结构和性能。通过流变学分析和无侧限压缩试验研究了CTG凝胶的相转变和机械性能。CTG体系在体温下能够快速完成凝胶相转变（2min），并且凝胶化温度随CS-TGA和β-GP浓度的升高而降低。CTG凝胶的压缩模量为28~32kPa，高于CS-TGA凝胶体系。体外溶胀和降解实验表明，凝胶的降解时间在30天以上，扫描电子显微镜观察显示凝胶内部呈现空间多孔网络结构。凝胶的体外蛋白释放研究表明，CTG凝胶对于蛋白有良好的控释作用，无突释现象，基本符合一级释放动力学规律。体外细胞毒性、溶血性实验和组织病理实验均表明凝胶有良好的生物相容性。为了进一步提高CTG凝胶的温度响应性和可控性，我们在CTG凝胶基础上引入了聚乙二醇丙烯酸酯（PEGDA），形成了物理相互作用、Michael加成和二硫键三重交联网络的巯基化壳聚糖-聚乙二醇丙烯酸酯/β-甘油磷酸钠（CTGP）凝胶体系，克服了CTG凝胶化时间不可控的缺点。通过改变凝胶中PEGDA的相对分子质量的大小，在改变凝胶化时间的同时进一步提高了体系的温度响应性，使得该凝胶体系的凝胶化时间可控。机械强度测试的结果与流变学测试的结果一致，CTGP凝胶的机械强度显著提高，其中以分子量700的PEGDA制备的CTGP700-4凝胶的压缩模量最高。以CTGP700-4凝胶为模型的进一步研究表明：CTGP凝胶比CTG凝胶具有更好的溶胀性能，且降解和体内实验结果证明该凝胶具有较高的稳定性，可以在体内外存留30天以上。以牛血清白蛋白为模型药物进行体外释放研究，结果表明：该凝胶对于牛血清白蛋白的控释效果明显，无突释现象，基本符合一级释放动力学规律。体外细胞毒性试验、溶血实验和组织病理实验均表明凝胶有很好的生物相容性。蛋白递送和组织工程领域均需要生物相容性良好，凝胶化时间可控并且机械强度和持久性较高的载体材料，，因此，具有三重交联结构的CTGP凝胶体系有着很好的应用前景。
[Abstract]:Chitosan based hydrogels have a good prospect in the field of drug controlled release and tissue engineering. In order to improve the performance and biocompatibility of chitosan based hydrogels, mercapto chitosan was prepared in this paper. The mercaptochitosan / 尾 -glycerophosphate (尾 -glycerophosphate) gel was prepared by physical and chemical double crosslinking networks. The structure and properties of CTG gel were studied. The phase transition and mechanical properties of CTG gel were studied by rheological analysis and unconfined compression test. CTG system could quickly complete the phase transition of CTG gel at body temperature for 2 mins, and the gelation temperature decreased with the increase of CS-TGA and 尾 -GP concentration. The compression modulus of the adhesive is 28 ~ 32 KPA, which is higher than that of CS-TGA gel system. In vitro swelling and degradation experiments showed that the degradation time of the gel was more than 30 days, and the scanning electron microscope (SEM) showed that the internal gel showed a porous network structure. The in vitro protein release of the gel showed that the CTG gel had a good controlled release effect on the protein, and there was no sudden release, which basically accords with the first-order release kinetics. In vitro cytotoxicity, hemolysis and histopathology showed that the gel had good biocompatibility. In order to further improve the temperature response and controllability of CTG gel, On the basis of CTG gel, we introduced polyethylene glycol acrylate (PEGDAN) to form a mercapto chitosan / 尾 -glycerol sodium phosphate gel system, which was formed by physical interaction and triplex cross-linking network of disulfide bonds. It overcomes the shortcoming that the gelation time of CTG is not controllable. By changing the relative molecular weight of PEGDA in the gel, the gelation time is changed and the temperature response of the gel system is further improved, which makes the gelation time of the gel system controllable. The results of mechanical strength test are consistent with those of rheological test. The mechanical strength of CTGP gel is significantly improved, and the compression modulus of CTGP700-4 gel prepared with molecular weight 700 PEGDA is the highest. Further studies using CTGP700-4 gel as a model show that the CTGP700-4 gel has better swelling performance than that of CTG gel, and the degradation and in vivo experimental results show that the gel has high stability and can remain in vivo and in vitro for more than 30 days. The in vitro release of bovine serum albumin (BSA) was studied. The results showed that the gel had obvious effect on the controlled release of bovine serum albumin (BSA) and had no sudden release phenomenon, which was basically in accordance with the first-order release kinetics. In vitro cytotoxicity test, hemolysis test and histopathological test showed that the gel had good biocompatibility. Protein delivery and tissue engineering require carrier materials with good biocompatibility, controllable gelation time and high mechanical strength and durability. Therefore, the CTGP gel system with triple cross-linked structure has a good prospect of application.
【学位授予单位】：天津大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：TQ460.1;R318.08

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