本文選題：柞蠶絲素 + 自組裝��； 參考：《東華大學(xué)》2012年碩士論文

【摘要】：柞蠶絲素是一種天然蛋白質(zhì),有良好的生物相容性及可降解性,常見其被應(yīng)用在手術(shù)縫合線、軟接觸透鏡、組織工程、傷口敷料以及藥物緩釋材料等方面,改變了柞蠶絲的傳統(tǒng)應(yīng)用。柞蠶絲素的降解產(chǎn)物對機(jī)體無毒,不易引起炎癥和免疫排斥反應(yīng)。鑒于這些特點,制作負(fù)載藥物的微球及組織工程支架具有很好的醫(yī)學(xué)應(yīng)用前景。 研究柞蠶絲素自組裝及其在藥物緩釋方面的應(yīng)用。分子自組裝就是在平衡條件下,分子間通過非共價相互作用自發(fā)組合形成的一類結(jié)構(gòu)明確、穩(wěn)定、具有某種特定功能或性能的分子聚集體或超分子結(jié)構(gòu)的過程。緩釋控釋給藥系統(tǒng)是指在控釋制劑的作用下藥物按零級速率或接近恒速釋放,以得到更平穩(wěn)的血藥濃度。 在本論文的研究中,我們開發(fā)出了一種新穎的方法,使絲素蛋白在特定條件下通過自組裝形成具有規(guī)整結(jié)構(gòu)的蛋白基納米微球和多孔支架材料,并對其臨床醫(yī)學(xué)應(yīng)用進(jìn)行了前期研究,主要內(nèi)容是柞蠶絲素利用低毒無毒的溶劑誘導(dǎo)制備微球及多孔支架以及其在藥物緩釋上的應(yīng)用。 柞蠶絲素在乙醇的誘導(dǎo)及冷凍條件下制備柞蠶絲素微球,我們利用顯微鏡、場發(fā)射電鏡、動態(tài)光散射、激光粒度儀、紅外等儀器來測試自組裝微球的形貌、粒徑及內(nèi)部結(jié)構(gòu),結(jié)果表明隨著乙醇的增加,微球的粒徑逐漸減小,結(jié)晶度相對提高,場發(fā)射電鏡表明微球的表面是凸凹不平的結(jié)構(gòu)。乙醇加入量為9ml時,平均粒徑是184.52nm,分散指數(shù)0.2903,這是最理想的微球分布。 采用掃描電鏡觀察了多孔支架的截面形態(tài),具有規(guī)整的開孔式結(jié)構(gòu),空隙間相互貫通,具有較好的力學(xué)性能。多孔支架隨柞蠶絲素溶液濃度的增加,其厚度增加,結(jié)晶度提高,孔徑逐漸變得小而均勻,孔隙率高達(dá)80%,孔徑在10～225μm之間�？伤苄院玫淖跣Q絲素溶液制備的多孔支架由模具外形來決定其結(jié)構(gòu)。柞蠶絲素溶液濃度大的構(gòu)象轉(zhuǎn)變程度變高,支架骨架的堆積也致密,絲素Ⅱ的成分增加,強(qiáng)度也有增大的趨勢。隨著濃度的增加,絲素Ⅱ的X-衍射角主要集中分布在17.2°,19.72°和29.42°。 我們對自組裝制備的絲素蛋白微球以及多孔支架在生物醫(yī)藥方面--藥物緩釋的應(yīng)用進(jìn)行了初步研究,明顯延長了藥物的釋放時間。藥物釋放過程分為兩個階段：初期的快速釋放階段和后期的緩慢釋放階段,這就大大降低了臨床藥物的副作用,提高了藥物的效率。5-Fu負(fù)載絲素蛋白多孔支架的藥物負(fù)載率和載藥率都略高于微球。 柞蠶絲素自組裝形成的微球和多孔支架在藥物緩釋方面具有很好的應(yīng)用前景,為我們的后續(xù)研究提供了好的基礎(chǔ)。
[Abstract]:Tussah silk fibroin is a natural protein, which has good biocompatibility and biodegradability. It is commonly used in surgical suture, soft contact lens, tissue engineering, wound dressing and drug release material. It has changed the traditional application of tussah silk. The degradation products of tussah silk fibroin are nontoxic to the body and are not easy to cause inflammation and immune rejection. In view of these characteristics, the preparation of loaded microspheres and tissue engineering scaffolds have good prospects for medical applications.
The self-assembly of tussah silk fibroin and its application in drug release. Molecular self-assembly is a process of molecular aggregation, stable, with certain specific functions or properties, formed by the spontaneous combination of non covalent interactions between molecules under equilibrium conditions. The release of the drug is controlled at zero or near constant speed to achieve a more stable blood concentration.
In this study, we developed a novel method to make silk fibroin protein based nanospheres and porous scaffolds with regular structure by self assembly under specific conditions, and to study the clinical application of silk fibroin. The main content is the preparation of tussah silk fibroin in the use of low toxicity and non-toxic solvent. Microspheres and porous scaffolds and their application in drug delivery.
Tussah silk fibroin was prepared under the conditions of ethanol induction and freezing to prepare tussah silk fibroin microspheres. We used microscopes, field emission electron microscopy, dynamic light scattering, laser particle size instrument, infrared and other instruments to test the morphology, particle size and internal structure of the self assembled microspheres. The results showed that the particle size of the microspheres decreased and the crystallinity increased with the increase of ethanol. The field emission electron microscope shows that the surface of the microspheres is a convex and concave structure. When the amount of ethanol is 9ml, the average particle size is 184.52nm and the dispersion index is 0.2903. This is the ideal microsphere distribution.
Scanning electron microscope (SEM) has been used to observe the cross section of porous scaffold, with a regular open hole structure with good mechanical properties. The thickness of porous scaffold increases with the concentration of tussah silk fibroin, its thickness increases, the pore size becomes smaller and even, the porosity is up to 80% and the pore size is 10~225 m. The structure of the porous scaffold prepared by the plastic silk fibroin solution is determined by the shape of the mold. The conformation transformation degree of the tussah silk fibroin solution is high, the accumulation of scaffold skeleton is also dense, the composition of silk fibroin II is increased and the strength of the silk fibroin II is increased. The X- diffraction angle of the silk fibroin II is mainly concentrated in 17.2 degrees, 19 .72 and 29.42 degrees.
A preliminary study of the application of self assembled silk fibroin microspheres and porous scaffolds in biopharmaceutical sustained-release was preliminarily studied, which significantly extended the release time of the drug. The drug release process was divided into two stages: the initial rapid release stage and the later slow release stage, which greatly reduced the clinical drug. Side effects enhanced the efficiency of drugs. The loading rate and drug loading rate of.5-Fu loaded porous silk fibroin scaffolds were slightly higher than that of microspheres.
The microspheres and porous scaffolds formed by self assembly of tussah silk fibroin have a good application prospect in drug delivery, and provide a good foundation for our follow-up research.

【學(xué)位授予單位】：東華大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R318.08

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