摘要
目前,生物可降解高分子药物载体是一大研究热点。生物可降解高分子药物载体可以通过在体内降解成小分子然后通过新陈代谢排除体外,同时可以通过控制材料的降解速率来控制药物释放速度。以两亲性嵌段共聚物胶束作为药物载体可以增加抗肿瘤药物的溶解性,减少其毒副作用。本文设计合成了两亲性树枝状聚酯作为为药物载体,来实现对药物进行控制释放,其具体内容如下:
1.首先合成了结构精确的羟基乙酸齐聚物以及羟基乙酸乳酸交替齐聚物,其中以溴为羟基封端取代基团,以叔丁基作为羧基保护基团。通过质子核磁共振(1H NMR)对其结构进行表征。
2.以四氢呋喃为溶剂,碳酸氢钾存在下,DMPA与齐聚物反应,得到支化单体。并通过质子核磁共振(~1H NMR)对其结构进行表征。
3.支化单体与4-苯甲氧基-4-氧代丁酸通过醇酸缩合反应将支化单元的末端保护,在三氟乙酸(TFA)的存在下脱去叔丁基,使其带有活性的羧基,然后通过收敛法合成树枝状大分子,并采用质子核磁共振(~1H NMR)对其结构进行了表征。
4.得到的树枝状大分子与聚乙二醇单甲醚进行缩合得到两亲性树枝状聚合物,并采用质子核磁共振(~1H NMR),MALDI-TOF MS以及凝胶色谱仪(GPC)对其进行表征。
5.对两亲性树枝状聚合物的胶束化进行研究,并通过荧光分光光度计,DLS,TEM对其进行表征;将两亲性树枝状聚酯作为抗肿瘤药物紫杉醇的载体,并通过DLS,TEM对其进行了表征,通过紫外分光光度计对其降解行为进行研究。
Recently, the study of the biodegradable polymer drug delivery attracts more people’s attention. The biodegradable polymer using as drug delivery can be degraded into water and carbon dioxide which were excreted body by metabolism; meantime, through control the degradation of the polymer materials, we can control the release of drugs. Polymer micelles can be formed through self-assemble of amphiphilic copolymer in aqueous environments. Polymer micelles as drug delivery can solubilize poorly water-soluble drugs in their inner core, decrease side effect. This article is focused on the synthesis and characterization of a novel biodegradable and amphiphilic dendritic polyester and using it as drug carrier. The research was mainly concerned with the following aspects:
1. First, the glycolic acid oligomer and glycolic acid-lactic acid alternate oligomer were synthesized; the carboxyl group of the oligomer was protected by tert-butyl group. The structure was characterized by 1H NMR.
2. In the presence of potassium bicarbonate in tetrahydrofuran, DMPA reacted with oligomer to synthesize the growing unit. The structure was characterized by 1H NMR.
3. The growing units reacted with 4-Benzyloxy-4-oxobutanoic acid in order to protect the hydroxyl of DMPA. The carboxyl of the growing units was activated in the presence of TFA. The dendrimer was synthesized through convergence method, and their structures were confirmed by 1H NMR.
4. The amphiphilic dendritic polymer was synthesized by condensation reaction of dendrimer and MPEG. The structure was characterized by 1H NMR, MALDI-TOF and GPC.
5. Micelle with core-shell structure was prepared in aqueous solution from the amphiphilic block copolymers, and characterized by 1H NMR, TEM, DLS and fluorescence. The block copolymer micelle was loaded with the water-fast anticancer drug; paclitaxel was also characterized by TEM and DLS. The release of paclitaxel from mPEG5000-G3-Bn was monitored by UV-Vis which showed that the release was controlled by a combined degradation-diffusion mechanism.
引文
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