【作者】 郭莉；

【导师】 景欢旺；

【作者基本信息】 兰州大学 ， 化学工程， 2011， 硕士

【摘要】 近年来,响应性聚合物胶束作为药物载体在生物材料领域引起了人们的高度重视,得到了广泛的研究和应用。由于人体病变部位及肿瘤组织周围的pH均低于正常组织,而温度却略高于正常体温,所以为了能更好地靶向治疗各种恶性肿瘤,具有温度和pH敏感型的智能释药系统被广泛地应用在药物载体研究方面。本文利用可逆加成断裂链转移自由基聚合方法,成功地制备了以聚甲基丙烯酸甲酯(PMMA)为疏水性内核,聚丙烯酸-b-聚异丙基丙烯酰胺(PAA-b-PNIPAM)为亲水性外壳的具有核-壳结构的两亲嵌段共聚物聚甲基丙烯酸甲酯-b-聚丙烯酸-co-聚异丙基丙烯酰胺(PMMA-b-(PAA-co-PNIPAM)。此嵌段共聚物以聚异丙基丙烯酰胺作为温度敏感段、以聚丙烯酸作为pH敏感段,具有温度、pH值双重敏感性。利用傅立叶红外光谱、核磁共振和透射电镜研究了聚合物的结构特征,用GPC测定了其分子量和分子量分布。透射电镜、激光粒度分析仪和动态光散射结果表明嵌段共聚物在水溶液中能够自组装形成直径为200nm的胶束颗粒。通过紫外-可见分光光度计和差示扫描量热法测得了不同pH值下嵌段共聚物的低临界溶解温度(lower critical solution temperature, LCST)。经过接枝后的嵌段共聚物的LCST比PNIPAM要高,且随着pH值的降低,聚合物的LCST随之降低。聚合物的LCST可以通过AA链段与NIPAM链段的比例、温度、pH值来控制。我们以嵌段共聚物PMMA-b-(PAA-co-PNIPAM)为载体,成功负载了抗癌药物紫杉醇,模拟了这种载药胶束在人体环境中的控释行为。结果表明载药胶束在人体正常生理温度(37℃)和病变温度(40℃)下的释放速率和累积释放量都要比室温下大很多。此嵌段共聚物兼具温度、pH值双重敏感性,将在药物缓释方面有潜在的应用前景。更多还原

【Abstract】 In recent years, the stimuli-sensitive polymeric micelles have received extensive attention and actively investigated for the preparation of intelligent drug carriers in biomedical application in the past several decades. When the body has inflammation or malignant tumour, the pH value would decline in this area. At the same time, the temperature is higher than normal tissue. Thus, properly designed carriers that are dual-responsive to both temperature and pH may be able to intelligently distinguish between normal and pathological tissues, achieving better targeting and treatment efficacy. In this paper, poly(methyl methacrylate)-b- (poly(crylic acid)-b-poly(N-isopropylacrylamide)) (PMMA-b-(PAA-co-PNIPAM)) which has a core-shell structure with the hydrophobic inner core (PMMA) and the hydrophilic shell (PNIPAM) is prepared by reversible addition-fragmentation transfer (RAFT) radical polymerization. The block copolymer (PMMA-b-(PAA-co-PNIPAM)) comprised PNIPAM as the Thermo- sensitive block and PAA as pH-sensitive block.The products are characterized by FT-IR,1H NMR spectra, TEM and GPC. The copolymers can undergo supramolecular self-assembly to thermo-response nanosized micelles in aqueous media. The sizes of the micelles are determined by transmission electron microscopy (TEM), granularity analysis and dynamic light scattering instrument (DLS). The micelles are regularly spherical in shape with an average hydrodynamic diameter around 200 nm. The lower critical solution temperature (LCST) of the copolymer which is higher than PNIPAM is measured by UV-vis and differential scanning calorimetry (DSC). The LCST is decreased by reducing the pH and which can adjust by changing the ratio of the A A and NIPAM, temperature and pH.We also study the drug delivery behaviors of the embedding of this anti-caneer drug paclitaxel (PTX) micelles in a simulated human body environment. The release speed and quantity of the micelles in natural body temperature (37℃) and malignant temperature (40℃) are more than 25℃. This block polymer have double sensitivity of temperature and pH, and it has a potential application prospect in the aspect of Drug slow-release.更多还原