本文選題：巰基化殼聚糖 + β-甘油磷酸鈉��； 參考：《天津大學(xué)》2012年碩士論文

【摘要】：殼聚糖基水凝膠在藥物緩控釋和組織工程領(lǐng)域具有很好的應(yīng)用前景，為了改善殼聚糖基水凝膠的應(yīng)用性能和生物相容性，本文制備了巰基化殼聚糖，并采用了物理和化學(xué)雙重交聯(lián)網(wǎng)絡(luò)制備了巰基化殼聚糖/β-甘油磷酸鈉（CTG）凝膠，研究了CTG凝膠的結(jié)構(gòu)和性能。通過流變學(xué)分析和無側(cè)限壓縮試驗(yàn)研究了CTG凝膠的相轉(zhuǎn)變和機(jī)械性能。CTG體系在體溫下能夠快速完成凝膠相轉(zhuǎn)變（2min），并且凝膠化溫度隨CS-TGA和β-GP濃度的升高而降低。CTG凝膠的壓縮模量為28~32kPa，高于CS-TGA凝膠體系。體外溶脹和降解實(shí)驗(yàn)表明，凝膠的降解時(shí)間在30天以上，掃描電子顯微鏡觀察顯示凝膠內(nèi)部呈現(xiàn)空間多孔網(wǎng)絡(luò)結(jié)構(gòu)。凝膠的體外蛋白釋放研究表明，CTG凝膠對(duì)于蛋白有良好的控釋作用，無突釋現(xiàn)象，基本符合一級(jí)釋放動(dòng)力學(xué)規(guī)律。體外細(xì)胞毒性、溶血性實(shí)驗(yàn)和組織病理實(shí)驗(yàn)均表明凝膠有良好的生物相容性。 為了進(jìn)一步提高CTG凝膠的溫度響應(yīng)性和可控性，我們?cè)贑TG凝膠基礎(chǔ)上引入了聚乙二醇丙烯酸酯（PEGDA），形成了物理相互作用、Michael加成和二硫鍵三重交聯(lián)網(wǎng)絡(luò)的巰基化殼聚糖-聚乙二醇丙烯酸酯/β-甘油磷酸鈉（CTGP）凝膠體系，克服了CTG凝膠化時(shí)間不可控的缺點(diǎn)。通過改變凝膠中PEGDA的相對(duì)分子質(zhì)量的大小，在改變凝膠化時(shí)間的同時(shí)進(jìn)一步提高了體系的溫度響應(yīng)性，使得該凝膠體系的凝膠化時(shí)間可控。機(jī)械強(qiáng)度測(cè)試的結(jié)果與流變學(xué)測(cè)試的結(jié)果一致，CTGP凝膠的機(jī)械強(qiáng)度顯著提高，其中以分子量700的PEGDA制備的CTGP700-4凝膠的壓縮模量最高。以CTGP700-4凝膠為模型的進(jìn)一步研究表明：CTGP凝膠比CTG凝膠具有更好的溶脹性能，且降解和體內(nèi)實(shí)驗(yàn)結(jié)果證明該凝膠具有較高的穩(wěn)定性，可以在體內(nèi)外存留30天以上。以牛血清白蛋白為模型藥物進(jìn)行體外釋放研究，結(jié)果表明：該凝膠對(duì)于牛血清白蛋白的控釋效果明顯，無突釋現(xiàn)象，基本符合一級(jí)釋放動(dòng)力學(xué)規(guī)律。體外細(xì)胞毒性試驗(yàn)、溶血實(shí)驗(yàn)和組織病理實(shí)驗(yàn)均表明凝膠有很好的生物相容性。蛋白遞送和組織工程領(lǐng)域均需要生物相容性良好，凝膠化時(shí)間可控并且機(jī)械強(qiáng)度和持久性較高的載體材料，，因此，具有三重交聯(lián)結(jié)構(gòu)的CTGP凝膠體系有著很好的應(yīng)用前景。
[Abstract]:Chitosan based hydrogels have a good prospect in the field of drug controlled release and tissue engineering. In order to improve the performance and biocompatibility of chitosan based hydrogels, mercapto chitosan was prepared in this paper. The mercaptochitosan / 尾 -glycerophosphate (尾 -glycerophosphate) gel was prepared by physical and chemical double crosslinking networks. The structure and properties of CTG gel were studied. The phase transition and mechanical properties of CTG gel were studied by rheological analysis and unconfined compression test. CTG system could quickly complete the phase transition of CTG gel at body temperature for 2 mins, and the gelation temperature decreased with the increase of CS-TGA and 尾 -GP concentration. The compression modulus of the adhesive is 28 ~ 32 KPA, which is higher than that of CS-TGA gel system. In vitro swelling and degradation experiments showed that the degradation time of the gel was more than 30 days, and the scanning electron microscope (SEM) showed that the internal gel showed a porous network structure. The in vitro protein release of the gel showed that the CTG gel had a good controlled release effect on the protein, and there was no sudden release, which basically accords with the first-order release kinetics. In vitro cytotoxicity, hemolysis and histopathology showed that the gel had good biocompatibility. In order to further improve the temperature response and controllability of CTG gel, On the basis of CTG gel, we introduced polyethylene glycol acrylate (PEGDAN) to form a mercapto chitosan / 尾 -glycerol sodium phosphate gel system, which was formed by physical interaction and triplex cross-linking network of disulfide bonds. It overcomes the shortcoming that the gelation time of CTG is not controllable. By changing the relative molecular weight of PEGDA in the gel, the gelation time is changed and the temperature response of the gel system is further improved, which makes the gelation time of the gel system controllable. The results of mechanical strength test are consistent with those of rheological test. The mechanical strength of CTGP gel is significantly improved, and the compression modulus of CTGP700-4 gel prepared with molecular weight 700 PEGDA is the highest. Further studies using CTGP700-4 gel as a model show that the CTGP700-4 gel has better swelling performance than that of CTG gel, and the degradation and in vivo experimental results show that the gel has high stability and can remain in vivo and in vitro for more than 30 days. The in vitro release of bovine serum albumin (BSA) was studied. The results showed that the gel had obvious effect on the controlled release of bovine serum albumin (BSA) and had no sudden release phenomenon, which was basically in accordance with the first-order release kinetics. In vitro cytotoxicity test, hemolysis test and histopathological test showed that the gel had good biocompatibility. Protein delivery and tissue engineering require carrier materials with good biocompatibility, controllable gelation time and high mechanical strength and durability. Therefore, the CTGP gel system with triple cross-linked structure has a good prospect of application.
【學(xué)位授予單位】：天津大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：TQ460.1;R318.08

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 崔媛;段潛;李艷輝;;透明質(zhì)酸的研究進(jìn)展[J];長(zhǎng)春理工大學(xué)學(xué)報(bào)(自然科學(xué)版);2011年03期

2 黃建艷;包磊;毛萱;葉巧巧;湯順清;;瓊脂糖-透明質(zhì)酸共聚物作為胰島素載體[J];材料科學(xué)與工程學(xué)報(bào);2009年01期

3 羅芳;;生物醫(yī)用水凝膠材料的研究進(jìn)展[J];廣東化工;2011年08期

4 彭順金;李建宗;武利民;;微懸浮聚合制備含氟丙烯酸酯/丙烯酸酯共聚物膠乳[J];高分子材料科學(xué)與工程;2006年06期

5 章蘇寧,陳濤,林嘉平,林紹梁,劉昌勝,湯冬梅,田曉慧;聚肽的結(jié)構(gòu)性能及其在生物材料領(lǐng)域的應(yīng)用[J];高分子通報(bào);2004年03期

6 劉鋒，卓仁禧;水凝膠的制備及應(yīng)用[J];高分子通報(bào);1995年04期

7 李進(jìn)進(jìn);朱南康;陳國(guó)強(qiáng);;醫(yī)用水凝膠的研究進(jìn)展[J];國(guó)外絲綢;2009年03期

8 盧國(guó)冬;燕青芝;宿新泰;劉中清;葛昌純;;多孔水凝膠研究進(jìn)展[J];化學(xué)進(jìn)展;2007年04期

9 徐露,曾慶孝,張立彥;“智能”凝膠的合成及其在生物領(lǐng)域的應(yīng)用[J];食品與機(jī)械;2005年04期

10 李作為;張立彥;曾慶孝;;琥珀�；瘹ぞ厶悄さ闹苽浼捌鋚H敏感型性研究[J];食品工業(yè)科技;2009年01期

本文編號(hào)：1895759