基于二硫键和酯键交联剂的可降解微凝胶的合成、结构调控及降解行为研究
发布时间：2019-01-17 12:14
【摘要】：微凝胶是尺寸在1nm-1μm的交联粒子,因其尺寸可调、表面可功能化及内部网络结构丰富的特点而非常适合用作药物载体。而可降解材料用于药物载体时一方面可以控制药物释放速率,另一方面降解之后的产物可以排除人体外,减少长期留存在人体内的风险,所以理想药物载体需具备可降解的性质。本论文研究了基于含可降解二硫键的交联剂的微凝胶的合成、降解性能及对药物的包载与释放行为和基于含酯键交联剂的微凝胶的合成及降解性能。在第一部分工作中,以N-异丙基丙烯酰胺(NIPAm)为主单体,过硫酸钾(KPS)为引发剂,N,N'-双丙烯酰胱胺(BAC)为交联剂,2-丙烯酰胺基-2-甲基丙磺酸钠盐(AMPS-Na)为带负电荷共单体,通过在NIPAm引发之后加入交联剂BAC,再加入AMPS-Na的方式合成了稳定的微凝胶,并研究了加入BAC的时机对微凝胶结构的影响,以及加入AMPS-Na的时机对微凝胶在磷酸缓冲液中的稳定性的影响。结果表明,这种在单体引发之后加入交联剂的方法可以得到窄分布粒径的微凝胶,随着BAC在NIPAm引发之后5 min加入变为15min后加入,微凝胶的Rg/Rh值由0.642变为1.020,所得到的的微凝胶的网络结构中心交联程度逐渐降低,微凝胶逐渐由实心球变为空心球的结构,至最终不能形成完整交联的微凝胶粒子。微凝胶在磷酸缓冲液(PBS)中的稳定性可以通过改变加入AMPS-Na的时间获得改善,AMPS-Na在BAC加入之后4 min和6 min时加入可以获得在25 ℃到49 ℃范围内稳定的微凝胶,而AMPS-Na在BAC加入之后8 min时加入,所得微凝胶在温度高于31 ℃时不稳定而发生聚集。微凝胶的降解程度随着BAC加入时间的延长而增加,而且在DL-1,4-二硫苏糖醇(DTT)存在下,降解程度大的微凝胶中包载的盐酸阿霉素(DOX)的释放速率要快于降解程度小的微凝胶。在第二部分工作中,我们用1,8-二氮杂二环[5.4.0]十一碳-7-烯(DBU)催化左旋丙交酯(LLA)开环聚合合成聚乳酸(PLLA),并进一步用PLLA与4-溴丁酰氯反应,合成了两个端基为Br的BrPLLABr。我们用NIPAm作为主单体,4-乙烯基吡啶(4-VP)作为共单体,用合成的BrPLLABr作为交联剂,通过4-VP和BrPLLABr发生季铵化反应的方式实现交联,合成了微凝胶。发现改变BrPLLABr的量对微凝胶的形貌和尺寸没有明显的影响,但是随着BrPLLABr的减少,微凝胶的温敏性逐渐增强。合成微凝胶可以在蛋白酶K的催化作用下降解。
[Abstract]:Microgel is a cross-linked particle with the size of 1nm-1 渭 m. Because of its adjustable size, functionalized surface and abundant internal network structure, microgel is very suitable for drug carrier. On the one hand, biodegradable materials can control the release rate of drugs when they are used as drug carriers, on the other hand, the products after degradation can be excluded from the human body and the risk of long-term retention in the human body can be reduced. Therefore, the ideal drug carrier should have degradable properties. In this paper, the synthesis, degradability, encapsulation and release behavior of microgels containing degradable disulfide bonds and the synthesis and degradation properties of microgels based on ester bond crosslinkers were studied. In the first part, N-isopropylacrylamide (NIPAm) was used as the main monomer, potassium persulfate (KPS) as the initiator, and NN-N-diacrylocysteine (BAC) as the crosslinking agent. Sodium 2-acrylamide 2-methylpropanesulfonate (AMPS-Na) was used as negative charge co-monomer to synthesize stable microgel by adding crosslinking agent BAC, and AMPS-Na after NIPAm initiation. The influence of the time of adding BAC on the structure of microgel and the stability of microgel in phosphoric acid buffer were also studied. The results showed that the microgel with narrow particle size could be obtained by adding crosslinking agent after monomer initiation. With the addition of BAC from 5 min to 15min after NIPAm initiation, the Rg/Rh value of microgel changed from 0.642 to 1.020. The degree of central crosslinking of the microgel network was gradually decreased, the microgel gradually changed from the solid sphere to the hollow sphere structure, and finally could not form a complete cross-linked microgel particles. The stability of microgels in phosphoric acid buffer (PBS) can be improved by changing the time of adding AMPS-Na. AMPS-Na can obtain stable microgels in the range of 25 鈩，
本文编号：2410048
[Abstract]:Microgel is a cross-linked particle with the size of 1nm-1 渭 m. Because of its adjustable size, functionalized surface and abundant internal network structure, microgel is very suitable for drug carrier. On the one hand, biodegradable materials can control the release rate of drugs when they are used as drug carriers, on the other hand, the products after degradation can be excluded from the human body and the risk of long-term retention in the human body can be reduced. Therefore, the ideal drug carrier should have degradable properties. In this paper, the synthesis, degradability, encapsulation and release behavior of microgels containing degradable disulfide bonds and the synthesis and degradation properties of microgels based on ester bond crosslinkers were studied. In the first part, N-isopropylacrylamide (NIPAm) was used as the main monomer, potassium persulfate (KPS) as the initiator, and NN-N-diacrylocysteine (BAC) as the crosslinking agent. Sodium 2-acrylamide 2-methylpropanesulfonate (AMPS-Na) was used as negative charge co-monomer to synthesize stable microgel by adding crosslinking agent BAC, and AMPS-Na after NIPAm initiation. The influence of the time of adding BAC on the structure of microgel and the stability of microgel in phosphoric acid buffer were also studied. The results showed that the microgel with narrow particle size could be obtained by adding crosslinking agent after monomer initiation. With the addition of BAC from 5 min to 15min after NIPAm initiation, the Rg/Rh value of microgel changed from 0.642 to 1.020. The degree of central crosslinking of the microgel network was gradually decreased, the microgel gradually changed from the solid sphere to the hollow sphere structure, and finally could not form a complete cross-linked microgel particles. The stability of microgels in phosphoric acid buffer (PBS) can be improved by changing the time of adding AMPS-Na. AMPS-Na can obtain stable microgels in the range of 25 鈩，
本文编号：2410048
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