透明质酸—阿魏酸靶向药物的合成及初步细胞学研究

发布时间：2018-06-27 18:34

  本文选题：阿魏酸 + 透明质酸　； 参考：《重庆医科大学》2014年硕士论文

【摘要】：目的以阿魏酸(FA)作为抗肿瘤药物模型，以透明质酸(HA)为靶向配体及载体制备透明质酸-阿魏酸(HA-FA)靶向药物；以高表达HA受体(CD44)的A549细胞和低表达HA受体(CD44)的HepG2细胞为实验细胞，考察HA-FA靶向药物对两种细胞的细胞毒性作用。 方法使用丝氨酸甲酯作为中间连接物合成HA-FA靶向药物；采用紫外分光光度法测定FA的结合率，采用1HNMR进行结构确证；以FA结合率作为检测指标用以考察HA-FA在不同温度下的稳定性；采用透析袋法考察HA-FA在不同释放介质(pH7.4及pH5.5的PBS)的体外释放情况；采用MTT法考察HA、FA及HA-FA对A549细胞和HepG2细胞的增殖抑制作用。 结果通过紫外扫描图可以初步证明HA-FA成功合成，采用1HNMR进行结构确证；采用紫外分光光度法测定FA与HA投料摩尔比为1:1时FA的结合率为16.58%；MTT实验结果显示，对高表达HA受体的A549细胞的增殖抑制作用为HAFAHA-FA，对低表达HA受体的HepG2细胞的增殖抑制作用为HAFA≈HA-FA。 结论本文采用UV法测定HA-FA中FA的结合率，方法简单可行。稳定性实验结果表明，HA-FA在4℃温度下相对较稳定。体外释放实验结果表明，，HA-FA靶向药物在不同释放介质(pH7.4及pH5.5的PBS)下FA的释放均有缓释效果。MTT实验结果显示，HA-FA对A549细胞的增殖抑制作用最强。以HA为靶向配体制备的HA-FA靶向药物可通过配体-受体特异性结合的机制将药物递送至靶部位，以提高药物对肿瘤细胞的增殖抑制作用。
[Abstract]:Objective to prepare hyaluronic acid-ferulic acid (HA-FA) targeted drugs by using ferulic acid (FA) as an antitumor drug model and hyaluronic acid (HA) targeted ligand and carrier, and to prepare hyaluronic acid-ferulic acid (HA-FA) targeted drugs in A549 cells with high expression of HA receptor (CD44) and HepG2 cells with low HA receptor (CD44) expression. To investigate the cytotoxic effects of HA-FA targeting drugs on two kinds of cells. Methods the target drugs of HA-FA were synthesized by using methyl serine as intermediate junctions, the binding rate of FA was determined by ultraviolet spectrophotometry, and the structure was confirmed by 1H NMR. The stability of HA-FA at different temperatures was investigated by using FA binding rate as the index, and the in vitro release of HA-FA in different release media (pH7.4 and pH5.5) was investigated by dialysis bag method. MTT assay was used to investigate the inhibitory effects of Hafa FA and HA-FA on the proliferation of A549 and HepG2 cells. Results the successful synthesis of HA-FA was proved by UV scanning, and the structure was confirmed by 1HNMR, and the binding ratio of FA to HA was determined by UV spectrophotometry when the molar ratio of FA to HA was 1:1. The results of MTT assay showed that the binding ratio of FA to HA was 16.58%. The inhibitory effect on the proliferation of A549 cells with high HA receptor expression was HAFAHA-FAA, and that on HepG2 cells with low HA receptor expression was HAFA 鈮

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