裝載小檗堿的羧甲基β-環(huán)糊精修飾的蒙脫石超分子網(wǎng)絡(luò)的抗菌活性
發(fā)布時(shí)間:2018-06-28 22:29
本文選題:超分子網(wǎng)絡(luò)材料 + 羧甲基環(huán)糊精。 參考:《重慶醫(yī)科大學(xué)》2017年碩士論文
【摘要】:本文采用廉價(jià)、簡(jiǎn)便、安全環(huán)保的合成方法,首次成功制備了羧甲基β-環(huán)糊精修飾的蒙脫石,然后通過(guò)分子間氫鍵自組裝成超分子網(wǎng)絡(luò)結(jié)構(gòu),并將其用于裝載小檗堿,提高鹽酸小檗堿的溶解度,改善其生物利用度,最終達(dá)到增強(qiáng)鹽酸小檗堿抗菌性能的目的。本研究?jī)?nèi)容主要包括以下兩個(gè)部分:第一部分:超分子網(wǎng)絡(luò)載體材料的制備、表征及載藥性能研究。采用β-環(huán)糊精在堿性條件下與一氯乙酸反應(yīng)合成羧甲基環(huán)糊精;對(duì)蒙脫石進(jìn)行硅烷化,得到三氨丙基三乙氧基硅烷修飾的蒙脫石;在室溫條件下通過(guò)1-(3-二甲氨基丙基)-3-乙基碳二亞胺鹽酸鹽和N-羥基琥珀酰亞胺催化,使羧甲基環(huán)糊精的羧基與三氨丙基三乙氧基硅烷硅烷化的蒙脫石上的伯胺基發(fā)生縮合反應(yīng),最終得到羧甲基環(huán)糊精修飾的蒙脫石超分子網(wǎng)絡(luò)材料。通過(guò)紅外光譜分析、熱重分析、X射線粉末衍射分析以及場(chǎng)發(fā)射掃描電鏡分析,對(duì)材料進(jìn)行了表征。采用鹽酸小檗堿作為模型藥物考查超分子網(wǎng)絡(luò)載體材料的體外載藥和釋放性能。結(jié)果:通過(guò)紅外光譜分析可知,超分子網(wǎng)絡(luò)材料在587,613和745cm-1出現(xiàn)了環(huán)糊精的特征峰,證明羧甲基環(huán)糊精對(duì)蒙脫石的成功嫁接;X射線粉末衍射分析顯示蒙脫石經(jīng)過(guò)修飾后特征峰左移,層空間擴(kuò)大,說(shuō)明羧甲基環(huán)糊精的嫁接反應(yīng)不僅發(fā)生在蒙脫石表面也發(fā)生在蒙脫石層間;熱重分析顯示,環(huán)糊精基團(tuán)在超分子網(wǎng)絡(luò)材料中的質(zhì)量占比為6.9%。應(yīng)用場(chǎng)發(fā)射掃描電鏡觀察超分子載體材料的獨(dú)特網(wǎng)絡(luò)結(jié)構(gòu)。體外載藥試驗(yàn)表明超分子網(wǎng)絡(luò)載體材料在50℃,p H7.0的條件下載藥5小時(shí)可達(dá)最大載藥量28.0%;體外釋放試驗(yàn)表明,在p H=7.4條件下,載藥超分子材料具有緩釋特征,在12小時(shí)內(nèi)釋放度可達(dá)49.3%。第二部分:載藥超分子網(wǎng)絡(luò)體外抗菌性能研究。采用稀釋平板法,比較載藥超分子網(wǎng)絡(luò)和游離藥物的體外抗菌性能。采用熒光顯微鏡觀察細(xì)菌對(duì)藥物的吸收,以考察載藥超分子材料抗菌能力的濃度依賴性。采用紫外分光光度計(jì)于600 nm處測(cè)定菌懸液的光密度,考查不同濃度的載藥超分子載體材料的長(zhǎng)期抗菌性能,應(yīng)用場(chǎng)發(fā)射掃描電鏡研究載藥超分子材料與細(xì)菌相互作用的機(jī)制。結(jié)果:經(jīng)過(guò)濃度分別為150、400μg/mL載藥超分子材料處理的金黃色葡萄球菌和大腸桿菌菌懸液,菌落總數(shù)從107下降到102,載藥超分子網(wǎng)絡(luò)材料的體外抗菌性能明顯優(yōu)于游離的藥物。平板稀釋計(jì)數(shù)法和熒光顯微鏡觀察,確證了載藥超分子網(wǎng)絡(luò)材料的抗菌性能隨濃度的增加而升高。不同濃度載藥超分子材料與細(xì)菌一起培育3天的光密度曲線顯示,載藥超分子材料具有長(zhǎng)效抑菌功能,對(duì)金黃色葡萄球菌的抑制率可達(dá)到97.81%,對(duì)大腸桿菌的抑制率達(dá)98.45%。
[Abstract]:In this paper, carboxymethyl 尾 -cyclodextrin modified montmorillonite was successfully prepared by a cheap, simple, safe and environmentally friendly method, and then self-assembled into supramolecular network structure by intermolecular hydrogen bonding, and used for loading berberine. To improve the solubility and bioavailability of berberine hydrochloride, the antibacterial activity of berberine hydrochloride was enhanced. The main contents of this study are as follows: the first part: preparation, characterization and drug loading properties of supramolecular network carrier materials. Carboxymethyl cyclodextrin was synthesized by the reaction of 尾 -cyclodextrin with monochloroacetic acid in alkaline condition, and montmorillonite modified by triaminopropyltriethoxysilane was obtained by silanizing montmorillonite. At room temperature, the carboxyl group of carboxymethyl cyclodextrin reacted with the primary group of triaminopropyl triethoxysilane on montmorillonite catalyzed by 1- (3-dimethylaminopropyl) -3-ethyl carbodiimide hydrochloride and N-hydroxysuccinimide. Finally, carboxymethyl cyclodextrin modified montmorillonite supramolecular network material was obtained. The materials were characterized by infrared spectroscopy, thermogravimetric analysis, X-ray powder diffraction and field emission scanning electron microscopy. Berberine hydrochloride was used as a model drug to investigate the drug loading and release properties of supramolecular network carrier in vitro. Results: the characteristic peaks of cyclodextrin appeared in 587613 and 745cm-1 of supramolecular network materials. It is proved that the successful grafting of montmorillonite with carboxymethyl cyclodextrin by X-ray powder diffraction shows that the characteristic peak of montmorillonite is shifted to the left and the layer space is enlarged after modification. The results show that the grafting reaction of carboxymethyl cyclodextrin occurs not only on the surface of montmorillonite but also on the interlayer of montmorillonite, and the mass ratio of cyclodextrin group in supramolecular network material is 6.9% by thermogravimetric analysis. The unique network structure of supramolecular carrier material was observed by field emission scanning electron microscope. The drug loading test in vitro showed that the supramolecular network carrier material could download the drug at 50 鈩,
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