本文選題：阿魏酸 + 透明質(zhì)酸　； 參考：《重慶醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的以阿魏酸(FA)作為抗腫瘤藥物模型，以透明質(zhì)酸(HA)為靶向配體及載體制備透明質(zhì)酸-阿魏酸(HA-FA)靶向藥物；以高表達(dá)HA受體(CD44)的A549細(xì)胞和低表達(dá)HA受體(CD44)的HepG2細(xì)胞為實(shí)驗(yàn)細(xì)胞，考察HA-FA靶向藥物對(duì)兩種細(xì)胞的細(xì)胞毒性作用。 方法使用絲氨酸甲酯作為中間連接物合成HA-FA靶向藥物；采用紫外分光光度法測定FA的結(jié)合率，采用1HNMR進(jìn)行結(jié)構(gòu)確證；以FA結(jié)合率作為檢測指標(biāo)用以考察HA-FA在不同溫度下的穩(wěn)定性；采用透析袋法考察HA-FA在不同釋放介質(zhì)(pH7.4及pH5.5的PBS)的體外釋放情況；采用MTT法考察HA、FA及HA-FA對(duì)A549細(xì)胞和HepG2細(xì)胞的增殖抑制作用。 結(jié)果通過紫外掃描圖可以初步證明HA-FA成功合成，采用1HNMR進(jìn)行結(jié)構(gòu)確證；采用紫外分光光度法測定FA與HA投料摩爾比為1:1時(shí)FA的結(jié)合率為16.58%；MTT實(shí)驗(yàn)結(jié)果顯示，對(duì)高表達(dá)HA受體的A549細(xì)胞的增殖抑制作用為HAFAHA-FA，對(duì)低表達(dá)HA受體的HepG2細(xì)胞的增殖抑制作用為HAFA≈HA-FA。 結(jié)論本文采用UV法測定HA-FA中FA的結(jié)合率，方法簡單可行。穩(wěn)定性實(shí)驗(yàn)結(jié)果表明，HA-FA在4℃溫度下相對(duì)較穩(wěn)定。體外釋放實(shí)驗(yàn)結(jié)果表明，，HA-FA靶向藥物在不同釋放介質(zhì)(pH7.4及pH5.5的PBS)下FA的釋放均有緩釋效果。MTT實(shí)驗(yàn)結(jié)果顯示，HA-FA對(duì)A549細(xì)胞的增殖抑制作用最強(qiáng)。以HA為靶向配體制備的HA-FA靶向藥物可通過配體-受體特異性結(jié)合的機(jī)制將藥物遞送至靶部位，以提高藥物對(duì)腫瘤細(xì)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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