【摘要】：在科學(xué)技術(shù)日新月異的21世紀(jì),隨著信息、能源、生物、環(huán)境等領(lǐng)域的迅速發(fā)展,其對相關(guān)材料都提出了更高的需求。而面向微納尺度的研究,已成為當(dāng)今各領(lǐng)域的熱點。微納材料由于本身較小的尺寸,使其具有了區(qū)別常規(guī)尺寸材料的特殊物理化學(xué)性質(zhì)。納米纖維是納米材料其中的一個重要分支,由于其具有良好的力學(xué)性能、傳導(dǎo)效應(yīng)和高比表面積等特點,受到了越來越多的重視和研究。靜電紡絲技術(shù)是一種傳統(tǒng)的簡單易行的制備微納高分子纖維的方法,通過對紡絲參數(shù)的調(diào)控,可以得到各種結(jié)構(gòu)和功能的纖維,在不同領(lǐng)域都展現(xiàn)出了應(yīng)用潛力。而微流控技術(shù)是一門多領(lǐng)域交叉的新興學(xué)科,其通過對微小流體的操控,可以得到各種微尺度結(jié)構(gòu)。其中微流控紡絲可以制備出直徑均勻且連續(xù)的纖維,已在組織工程和藥物運輸領(lǐng)域有所應(yīng)用�；诒菊n題組之前的研究成果,本文對微流控與靜電紡絲有機結(jié)合制備竹狀結(jié)構(gòu)纖維的方法進行簡單的調(diào)整和優(yōu)化。考察了竹狀結(jié)構(gòu)纖維膜孔隙率和吸水率的變化,并驗證了纖維空腔部分在運載質(zhì)粒方面的潛在應(yīng)用。之后將阿霉素和阿帕替尼兩種藥物載入纖維的不同部分,考證了載藥纖維對耐藥腫瘤的治療作用。第二章考察了竹狀結(jié)構(gòu)纖維膜的結(jié)構(gòu),并實現(xiàn)了一些潛在應(yīng)用。結(jié)果表明,由于纖維內(nèi)部存在空腔結(jié)構(gòu),且空腔中含有強吸水性物質(zhì)甘油。所以,制得纖維膜的孔隙率高于普通實心纖維膜,且吸水率是普通纖維膜的近2倍。將帶有綠色熒光蛋白的質(zhì)粒載入纖維空腔中,其活性能夠很好保持,并且通過細胞實驗進行了驗證。第三章為含有膠束的載雙藥竹狀結(jié)構(gòu)的纖維的制備與相應(yīng)的釋藥行為和體外抗腫瘤效果考察。首先考察了此種纖維的釋藥曲線,并采用多種手段解釋驗證了其釋放機理,即纖維空腔中的裸藥和載藥膠束會隨著空腔薄壁的降解和破壞而快速釋放,而纖維基體上的藥物只能隨著本身的緩慢降解而持續(xù)釋放。之后詳細考察了載雙藥的纖維在體外對于耐藥腫瘤細胞的抑制作用,并證明了該纖維材料起到了良好的逆轉(zhuǎn)耐藥和殺滅腫瘤細胞的功能。在上一章的基礎(chǔ)上,第四章中進行了載藥纖維在裸鼠體內(nèi)的藥物富集研究。事先在裸鼠皮下建立腫瘤模型。然后采用局部給藥的方法,將纖維埋植到了腫瘤組織附近的皮下。于不同的預(yù)定時間點檢測了活體裸鼠和離體各組織器官的藥物富集情況,成功驗證了載雙藥纖維可以有效促進化療藥物阿霉素在耐藥腫瘤組織中的累積。
[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.
【學(xué)位授予單位】：西南交通大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R943

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