發(fā)布時(shí)間：2019-01-21 16:14

【摘要】：可注射原位絲素（SF）水凝膠具有手術(shù)創(chuàng)傷微小的優(yōu)點(diǎn)，在各種生物材料中具有潛在的應(yīng)用優(yōu)勢(shì)。作為一種理想的可注射性原位水凝膠材料，自身需能夠快速凝膠化以滿足在體內(nèi)注射后凝膠能夠立即成型的需要。本文研究了兩類小分子的表面活性劑，即十二烷基硫酸鈉（SDS）、十二烷基醚硫酸鈉（AES）等硫酸酯鹽類陰離子表面活性劑和季銨鹽類陽(yáng)離子表面活性劑對(duì)家蠶絲素凝膠化、絲素凝膠結(jié)構(gòu)和性能的影響，并探討了相應(yīng)的絲素原位凝膠化機(jī)理。 硫酸酯鹽類陰離子表面活性劑能夠縮短絲素凝膠化的時(shí)間，且其對(duì)絲素凝膠化的促進(jìn)程度與自身疏水烴鏈長(zhǎng)度有著直接的關(guān)系，烴鏈較短（㩳8）時(shí)，對(duì)絲素凝膠化無(wú)明顯的促進(jìn)作用，而隨著烴鏈的延長(zhǎng)，相應(yīng)絲素的膠凝速度有增加的趨勢(shì)。詳細(xì)研究了SDS引發(fā)絲素快速凝膠化的機(jī)制，并對(duì)硫酸鹽類陰離子表面活性劑-絲素復(fù)合水凝膠的結(jié)構(gòu)和力學(xué)、降解、體外釋藥等性能進(jìn)行了表征。其中釋藥結(jié)果表明，，SDS、AES促發(fā)形成的(SDS/SF、AES/SF)凝膠對(duì)阿霉素這種模型藥物的體外釋放呈現(xiàn)出，前期（1-10天）釋放量較大且持續(xù)時(shí)間較長(zhǎng)，而后期（10-38天）釋放緩慢且速率較為恒定的特點(diǎn)，這種釋藥規(guī)律符合抗癌藥物的用藥原則，可用于構(gòu)建可注射絲素原位凝膠緩釋體系。 季銨鹽類抗菌劑作為凝膠促進(jìn)劑，能夠誘導(dǎo)絲素蛋白水溶液快速原位凝膠化。利用X射線衍射、紅外光譜、掃描電鏡、差熱分析和圓二色光譜等手段對(duì)所制絲素水凝膠的結(jié)構(gòu)、熱穩(wěn)定、降解性、抗菌性能及其形成機(jī)理進(jìn)行了探究。研究結(jié)果表明，季銨鹽促發(fā)形成的絲素水凝膠為β-折疊片層結(jié)構(gòu)，凝膠內(nèi)部形貌為多孔的三維網(wǎng)狀結(jié)構(gòu)，且對(duì)革蘭氏陽(yáng)性菌和陰性菌都有很明顯的抗菌效果。同時(shí)由體外降解、差熱分析結(jié)果可知，季銨鹽引發(fā)絲素蛋白溶液快速形成水凝膠，其三維交聯(lián)結(jié)構(gòu)在水中可以降解，在蛋白酶液中更容易降解。季銨鹽在水凝膠中主要以無(wú)定形或亞穩(wěn)態(tài)晶體狀態(tài)存在，容易擴(kuò)散釋放，達(dá)到較好的抗菌效果，這種抗菌性的原位絲素蛋白水凝膠有望可以用于外科傷口敷料。
[Abstract]:Injectable in situ fibroin (SF) hydrogel has the advantages of minimal surgical trauma and potential application in various biomaterials. As an ideal injectable in situ hydrogel material, it needs to be quickly gelatinized to meet the need of the gel forming immediately after injection in vivo. The gelation of silkworm fibroin by two kinds of small molecular surfactants, such as sodium dodecyl sulfate, sodium (SDS), sodium dodecyl ether sulfate, sodium (AES), and quaternary ammonium cationic surfactants, has been studied in this paper. The influence of the structure and properties of silk fibroin gel was discussed, and the mechanism of silk fibroin in situ gelation was discussed. Sulfate anionic surfactants can shorten the gelation time of silk fibroin, and its promotion degree is directly related to the length of its hydrophobic hydrocarbon chain, when the hydrophobic chain is short (? 8), The gelation rate of silk fibroin increased with the extension of hydrocarbon chain. The mechanism of rapid gelation of silk fibroin initiated by SDS was studied in detail. The structure, mechanical properties, degradation and in vitro release of sulfate anionic surfactant / silk fibroin composite hydrogel were characterized. The results of drug release showed that the release of adriamycin in vitro by SDS/SF,AES/SF gel stimulated by SDS,AES was relatively large in the early stage (1-10 days) and lasted for a long time. But in the late stage (10-38 days), the release was slow and the rate was constant. This release law was consistent with the principle of anti-cancer drugs, and could be used to construct the injectable silk fibroin in-situ gel sustained release system. Quaternary ammonium salts as gel promoters can induce rapid in situ gelation of silk fibroin solution. The structure, thermal stability, biodegradability, antibacterial properties and formation mechanism of silk fibroin hydrogel were investigated by means of X-ray diffraction, infrared spectroscopy, scanning electron microscope, differential thermal analysis and circular dichroism spectroscopy. The results showed that the silk fibroin hydrogel induced by quaternary ammonium salt was a 尾 -folded lamellar structure, and the internal morphology of the gel was a porous three-dimensional reticular structure, and it had obvious antibacterial effect against both Gram-positive and negative bacteria. At the same time, the results of in vitro degradation and differential thermal analysis showed that quaternary ammonium salt initiated the rapid formation of hydrogel in silk fibroin solution, its three-dimensional cross-linking structure could be degraded in water, and it was easier to degrade in protease solution. Quaternary ammonium salts exist mainly in amorphous or metastable crystal state in hydrogels, which are easy to diffuse and release to achieve better antibacterial effect. This antibacterial in situ fibroin hydrogel is expected to be used in surgical wound dressing.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R318.08

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 閔思佳,陳芳芳,田莉,朱良均;不同溫度下環(huán)氧化合物與絲素蛋白作用形成的凝膠結(jié)構(gòu)[J];蠶業(yè)科學(xué);2005年02期

2 解芳;邵惠麗;胡學(xué)超;;再生絲素水溶液在存放過程中的結(jié)構(gòu)變化[J];東華大學(xué)學(xué)報(bào)(自然科學(xué)版);2006年06期

3 周軒榕,盧滇楠,邵曼君,邢曉東,王曉工,劉錚;表面接枝季銨鹽型高分子材料抗菌過程的特性研究[J];高等學(xué)�；瘜W(xué)學(xué)報(bào);2003年06期

4 閔思佳,陳芳芳,吳豪翔;環(huán)氧化合物與絲素蛋白化學(xué)交聯(lián)凝膠的結(jié)構(gòu)[J];高等學(xué)校化學(xué)學(xué)報(bào);2005年05期

5 盧滇楠,周軒榕,邢曉東,王曉工,劉錚;表面接枝季銨鹽型聚合物的纖維素纖維——滅菌機(jī)理研究[J];高分子學(xué)報(bào);2004年01期

6 文建川;姚晉榮;邵正中;;非生理活性蛋白質(zhì)的研究進(jìn)展及其在材料領(lǐng)域中的應(yīng)用[J];高分子學(xué)報(bào);2011年01期

7 朱文,段世鋒,丁建東;組織工程用水凝膠材料[J];功能高分子學(xué)報(bào);2004年04期

8 周文;陳新;邵正中;;紅外和拉曼光譜用于對(duì)絲蛋白構(gòu)象的研究[J];化學(xué)進(jìn)展;2006年11期

9 張維穎,樊東輝,徐政,顧其勝;溫敏性殼聚糖凝膠的阿霉素藥物體外緩釋研究[J];中國(guó)海洋藥物;2005年05期

10 朱圓,曹偉新;外科傷口敷料的選擇[J];解放軍護(hù)理雜志;2005年04期

本文編號(hào)：2412811