pH敏感型基因及药物载体的制备及其性能研究
发布时间：2018-08-15 19:39
【摘要】：随着分子生物学及其相关学科的不断发展,针对传统治疗手段难以治愈的基因缺陷等疾病及传统药物治疗的毒副作用较大的问题,分别提出了基因治疗及靶向药物治疗的概念。而实现基因治疗及靶向药物治疗均离不开载体材料。本研究通过利用r-氨丙基三乙氧基硅烷(APTES)及其水解产物八臂氨基多面体硅氧烷(PNH)作为引导剂,分别制备得到了两类不同的载体材料,并对其相关性能进行研究。利用r-氨丙基三乙氧基硅烷(APTES)中氨基基团的正电性,及其与钙离子的结合特性,通过引导钙离子与碳酸根离子结合形成的碳酸钙纳米粒,并改变制备工艺条件,制备得到了不同形貌的碳酸钙载体材料,同时对其制备工艺原理进行相关探究。选择已制备的棒状碳酸钙粒子作为抗癌药物阿霉素载体,对其负载阿霉素药物前后的生物学性能、载药及药物释放性能进行研究。同时,选择制备的碳酸钙微球作为Osterix基因的转染载体,并对其相关性能进行研究。通过研究发现,棒状碳酸钙粒子作为阿霉素药物载体时,具有较高的药物负载性能。同时通过实验设计,实现其药物释放速率能够对药物载体所在释放环境的p H值具有显著的响应性。研究发现,所设计的负载药物的载体材料能够实现在中性条件下药物释放速率的显著降低。作为基因载体去实现基因转染的实验研究发现球形碳酸钙材料(r CCMP)能够实现一定的转染效率,具有作为基因转染载体材料的潜力。选取具有较好生物相容性的聚己内酯(PCL)作为主体材料,通过天冬氨酸(Asp)修饰PCL端基,然后与PNH进行分子自组装。通过分子自组装的方法制备了尺寸均一、较好分散性和较低生物毒性的PCL-Asp/PNH微球材料。利用制备得到的微球负载阿霉素药物,并对其药物负载能力及其在PBS缓冲液中的药物释放性能进行相关研究。研究发现,PCL-Asp/PNH微球载体材料对阿霉素药物的药物负载率在设计的条件下能够达到77.58%,且其在酸性条件下能够实现药物的持续释放。5天内的药物释放率达到77.16%,能够实现一定的缓释作用,但其在中性的PBS环境下,药物的释放率较低(不到20%)。
[Abstract]:With the development of molecular biology and its related disciplines, the concepts of gene therapy and targeted drug therapy have been put forward for diseases such as gene defects which can not be cured by traditional treatment methods and the large toxicity and side effects of traditional drug therapy. Both gene therapy and targeted drug therapy can not be achieved without carrier materials. In this study, two kinds of different carrier materials were prepared by using r-aminopropyltriethoxysilane (APTES) and its hydrolysate octa-arm aminopolyhedral siloxane (PNH) as the guiding agent, and their related properties were studied. According to the positive charge of amino group in r-aminopropyl triethoxy silane (APTES) and its binding property with calcium ion, calcium carbonate nanoparticles were formed by guiding calcium ion to combine with carbonate ion, and the preparation conditions were changed. Calcium carbonate carrier materials with different morphologies were prepared, and the preparation principle of calcium carbonate was studied. Rod calcium carbonate particles were selected as the carrier of adriamycin to study the biological properties, drug loading and drug release before and after loading adriamycin. At the same time, calcium carbonate microspheres were selected as the transfection vector of Osterix gene, and the related properties were studied. It was found that the rod-shaped calcium carbonate particles had high drug loading performance when they were used as drug carriers for doxorubicin. At the same time, the experimental design shows that the drug release rate can be significantly responsive to the pH value of the release environment where the drug carrier is located. It is found that the designed carrier material can significantly reduce the drug release rate under neutral conditions. As a gene vector to realize gene transfection, it was found that the spherical calcium carbonate material (r CCMP) could achieve a certain transfection efficiency, and had the potential as a gene transfection vector material. Polycaprolactone (PCL) with good biocompatibility was selected as the main material. The PCL terminal group was modified by aspartic acid (Asp) and then self-assembled with PNH. PCL-Asp/PNH microspheres with uniform size, good dispersion and low biotoxicity were prepared by molecular self-assembly. Doxorubicin was loaded with microspheres and its drug loading capacity and drug release in PBS buffer were studied. The results show that the drug loading rate of PCL-AspP / PNH microspheres can reach 77.58 under the designed conditions, and the drug release rate of PCL-AspP / PNH microspheres can reach 77.16% within 5 days after sustained release under acidic conditions. The drug delivery rate of PCL-Aspp / PNH microspheres can reach 77.58 in the designed condition, and the drug release rate can reach 77.16% in acidic condition. A certain slow release effect, But in neutral PBS, the drug release rate was lower (less than 20%).
【学位授予单位】：华南理工大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R318.08
本文编号：2185206
[Abstract]:With the development of molecular biology and its related disciplines, the concepts of gene therapy and targeted drug therapy have been put forward for diseases such as gene defects which can not be cured by traditional treatment methods and the large toxicity and side effects of traditional drug therapy. Both gene therapy and targeted drug therapy can not be achieved without carrier materials. In this study, two kinds of different carrier materials were prepared by using r-aminopropyltriethoxysilane (APTES) and its hydrolysate octa-arm aminopolyhedral siloxane (PNH) as the guiding agent, and their related properties were studied. According to the positive charge of amino group in r-aminopropyl triethoxy silane (APTES) and its binding property with calcium ion, calcium carbonate nanoparticles were formed by guiding calcium ion to combine with carbonate ion, and the preparation conditions were changed. Calcium carbonate carrier materials with different morphologies were prepared, and the preparation principle of calcium carbonate was studied. Rod calcium carbonate particles were selected as the carrier of adriamycin to study the biological properties, drug loading and drug release before and after loading adriamycin. At the same time, calcium carbonate microspheres were selected as the transfection vector of Osterix gene, and the related properties were studied. It was found that the rod-shaped calcium carbonate particles had high drug loading performance when they were used as drug carriers for doxorubicin. At the same time, the experimental design shows that the drug release rate can be significantly responsive to the pH value of the release environment where the drug carrier is located. It is found that the designed carrier material can significantly reduce the drug release rate under neutral conditions. As a gene vector to realize gene transfection, it was found that the spherical calcium carbonate material (r CCMP) could achieve a certain transfection efficiency, and had the potential as a gene transfection vector material. Polycaprolactone (PCL) with good biocompatibility was selected as the main material. The PCL terminal group was modified by aspartic acid (Asp) and then self-assembled with PNH. PCL-Asp/PNH microspheres with uniform size, good dispersion and low biotoxicity were prepared by molecular self-assembly. Doxorubicin was loaded with microspheres and its drug loading capacity and drug release in PBS buffer were studied. The results show that the drug loading rate of PCL-AspP / PNH microspheres can reach 77.58 under the designed conditions, and the drug release rate of PCL-AspP / PNH microspheres can reach 77.16% within 5 days after sustained release under acidic conditions. The drug delivery rate of PCL-Aspp / PNH microspheres can reach 77.58 in the designed condition, and the drug release rate can reach 77.16% in acidic condition. A certain slow release effect, But in neutral PBS, the drug release rate was lower (less than 20%).
【学位授予单位】：华南理工大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R318.08
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