基于微流控芯片的静电纺丝纤维制备及应用研究
发布时间：2019-05-08 09:05
【摘要】：在科学技术日新月异的21世纪,随着信息、能源、生物、环境等领域的迅速发展,其对相关材料都提出了更高的需求。而面向微纳尺度的研究,已成为当今各领域的热点。微纳材料由于本身较小的尺寸,使其具有了区别常规尺寸材料的特殊物理化学性质。纳米纤维是纳米材料其中的一个重要分支,由于其具有良好的力学性能、传导效应和高比表面积等特点,受到了越来越多的重视和研究。静电纺丝技术是一种传统的简单易行的制备微纳高分子纤维的方法,通过对纺丝参数的调控,可以得到各种结构和功能的纤维,在不同领域都展现出了应用潜力。而微流控技术是一门多领域交叉的新兴学科,其通过对微小流体的操控,可以得到各种微尺度结构。其中微流控纺丝可以制备出直径均匀且连续的纤维,已在组织工程和药物运输领域有所应用。基于本课题组之前的研究成果,本文对微流控与静电纺丝有机结合制备竹状结构纤维的方法进行简单的调整和优化。考察了竹状结构纤维膜孔隙率和吸水率的变化,并验证了纤维空腔部分在运载质粒方面的潜在应用。之后将阿霉素和阿帕替尼两种药物载入纤维的不同部分,考证了载药纤维对耐药肿瘤的治疗作用。第二章考察了竹状结构纤维膜的结构,并实现了一些潜在应用。结果表明,由于纤维内部存在空腔结构,且空腔中含有强吸水性物质甘油。所以,制得纤维膜的孔隙率高于普通实心纤维膜,且吸水率是普通纤维膜的近2倍。将带有绿色荧光蛋白的质粒载入纤维空腔中,其活性能够很好保持,并且通过细胞实验进行了验证。第三章为含有胶束的载双药竹状结构的纤维的制备与相应的释药行为和体外抗肿瘤效果考察。首先考察了此种纤维的释药曲线,并采用多种手段解释验证了其释放机理,即纤维空腔中的裸药和载药胶束会随着空腔薄壁的降解和破坏而快速释放,而纤维基体上的药物只能随着本身的缓慢降解而持续释放。之后详细考察了载双药的纤维在体外对于耐药肿瘤细胞的抑制作用,并证明了该纤维材料起到了良好的逆转耐药和杀灭肿瘤细胞的功能。在上一章的基础上,第四章中进行了载药纤维在裸鼠体内的药物富集研究。事先在裸鼠皮下建立肿瘤模型。然后采用局部给药的方法,将纤维埋植到了肿瘤组织附近的皮下。于不同的预定时间点检测了活体裸鼠和离体各组织器官的药物富集情况,成功验证了载双药纤维可以有效促进化疗药物阿霉素在耐药肿瘤组织中的累积。
[Abstract]:With the rapid development of information, energy, biology, environment and other fields in the 21st century with the rapid development of science and technology, there is a higher demand for related materials. The research of micro-and nano-scale has become a hot spot in various fields. Due to its small size, micro-nano materials have special physical and chemical properties which are different from conventional size materials. Nano-fiber is one of the important branches of nano-materials. Due to its good mechanical properties, conduction effect and high specific surface area, nano-fiber has been paid more and more attention and research. Electrospinning is a traditional and easy method to prepare micro / nano polymer fibers. By adjusting spinning parameters, various structures and functions of fibers can be obtained, and the potential applications in different fields have been demonstrated. Microfluidic technology is a multi-domain cross-cutting new subject, which can get various micro-scale structures through the manipulation of micro-fluids. Microfluidic spinning can produce fibers with uniform diameter and continuous diameter, which has been used in tissue engineering and drug transportation. Based on the previous research results of our research group, this paper simply adjusts and optimizes the method of preparing bamboo-like structural fibers by combining microfluidic with electrospinning. The changes of porosity and water absorption of bamboo-like fiber membrane were investigated, and the potential application of fiber cavity in carrying plasmid was verified. Doxorubicin and apatinib were loaded into different parts of the fibers to investigate the therapeutic effect of drug-loaded fibers on drug-resistant tumors. In the second chapter, the structure of bamboo-like fiber membrane is investigated, and some potential applications are realized. The results show that there is a cavity structure in the fiber and glycerol is a strong absorbent substance in the cavity. Therefore, the porosity of the prepared fiber membrane is higher than that of the ordinary solid fiber membrane, and the water absorption rate of the prepared fiber membrane is nearly 2 times as much as that of the ordinary fiber membrane. The plasmid containing green fluorescent protein was loaded into the fiber cavity and its activity was well maintained and was verified by cell experiment. In the third chapter, the preparation, drug release behavior and antitumor effect of bamboo-like fibers containing micelles were investigated. First, the drug release curve of this kind of fiber was investigated, and its release mechanism was verified by many methods. That is, the bare drug and drug-loaded micelles in the fiber cavity can be released rapidly with the degradation and destruction of the thin wall of the cavity. On the other hand, the drugs on the fiber matrix can only be released continuously with the slow degradation of itself. Then the inhibitory effect of the double-drug-loaded fibers on drug-resistant tumor cells in vitro was investigated in detail, and it was proved that the fiber material could reverse the drug-resistance and kill the tumor cells. On the basis of the previous chapter, the drug enrichment of drug-loaded fibers in nude mice was studied in chapter 4. The tumor model was established in nude mice subcutaneously. Then, by local administration, the fibers were implanted subcutaneously near the tumor tissue. Drug enrichment in nude mice and tissues and organs in vivo and in vitro was detected at different predetermined time points. It was successfully demonstrated that dual-drug-loaded fibers could effectively promote the accumulation of doxorubicin in drug-resistant tumor tissues.
【学位授予单位】：西南交通大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R943
本文编号：2471783
[Abstract]:With the rapid development of information, energy, biology, environment and other fields in the 21st century with the rapid development of science and technology, there is a higher demand for related materials. The research of micro-and nano-scale has become a hot spot in various fields. Due to its small size, micro-nano materials have special physical and chemical properties which are different from conventional size materials. Nano-fiber is one of the important branches of nano-materials. Due to its good mechanical properties, conduction effect and high specific surface area, nano-fiber has been paid more and more attention and research. Electrospinning is a traditional and easy method to prepare micro / nano polymer fibers. By adjusting spinning parameters, various structures and functions of fibers can be obtained, and the potential applications in different fields have been demonstrated. Microfluidic technology is a multi-domain cross-cutting new subject, which can get various micro-scale structures through the manipulation of micro-fluids. Microfluidic spinning can produce fibers with uniform diameter and continuous diameter, which has been used in tissue engineering and drug transportation. Based on the previous research results of our research group, this paper simply adjusts and optimizes the method of preparing bamboo-like structural fibers by combining microfluidic with electrospinning. The changes of porosity and water absorption of bamboo-like fiber membrane were investigated, and the potential application of fiber cavity in carrying plasmid was verified. Doxorubicin and apatinib were loaded into different parts of the fibers to investigate the therapeutic effect of drug-loaded fibers on drug-resistant tumors. In the second chapter, the structure of bamboo-like fiber membrane is investigated, and some potential applications are realized. The results show that there is a cavity structure in the fiber and glycerol is a strong absorbent substance in the cavity. Therefore, the porosity of the prepared fiber membrane is higher than that of the ordinary solid fiber membrane, and the water absorption rate of the prepared fiber membrane is nearly 2 times as much as that of the ordinary fiber membrane. The plasmid containing green fluorescent protein was loaded into the fiber cavity and its activity was well maintained and was verified by cell experiment. In the third chapter, the preparation, drug release behavior and antitumor effect of bamboo-like fibers containing micelles were investigated. First, the drug release curve of this kind of fiber was investigated, and its release mechanism was verified by many methods. That is, the bare drug and drug-loaded micelles in the fiber cavity can be released rapidly with the degradation and destruction of the thin wall of the cavity. On the other hand, the drugs on the fiber matrix can only be released continuously with the slow degradation of itself. Then the inhibitory effect of the double-drug-loaded fibers on drug-resistant tumor cells in vitro was investigated in detail, and it was proved that the fiber material could reverse the drug-resistance and kill the tumor cells. On the basis of the previous chapter, the drug enrichment of drug-loaded fibers in nude mice was studied in chapter 4. The tumor model was established in nude mice subcutaneously. Then, by local administration, the fibers were implanted subcutaneously near the tumor tissue. Drug enrichment in nude mice and tissues and organs in vivo and in vitro was detected at different predetermined time points. It was successfully demonstrated that dual-drug-loaded fibers could effectively promote the accumulation of doxorubicin in drug-resistant tumor tissues.
【学位授予单位】：西南交通大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R943
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