纳米棒状磷灰石蛋白药物载体的制备、表征及性能研究

发布时间：2018-08-16 09:13

【摘要】：具有生物相容性和生物活性的纳米磷灰石作为一种新型的药物载体，在药物控制释放领域有着很大的应用价值并得到广泛的研究。本论文采用模板-水热法合成介孔棒状纳米羟基磷灰石、采用溶胶-凝胶法合成棒状纳米锶羟基磷灰石并对纳米磷灰石的体外负载蛋白药物及缓释实验进行了研究。第一利用溶胶-凝胶法合成棒状纳米锶羟基磷灰石，，考察老化时间对掺锶磷灰石形成的影响，并采用XRD、FT-IR、SEM、TEM等测试方法对纳米锶羟基磷灰石进行表征。研究发现老化时间是决定样品形貌的关键因素，当老化温度为60°C、老化时间为48h时，制备的锶磷灰石呈棒状结构，其直径约为30nm，长度为120 180nm。第二利用模板-水热法合成介孔棒状纳米羟基磷灰石，考察表面活性剂(F127)用量对样品介孔的影响，采用XRD、FT-IR、SEM、EDX、TEM、BET等测试方法对纳米羟基磷灰石进行表征。结果表明制备的羟基磷灰石属于介孔材料并呈棒状结构且结晶度很高，颗粒直径大约为25nm，长度为75 125nm。当F127的用量为1.33g时，棒状磷灰石的比表面积为86.29m2g 1，平均孔容为0.27cm3g 1，平均孔径为3.83nm。第三对制备的介孔棒状纳米磷灰石进行载药性能研究。牛血清白蛋白(BSA)和溶菌酶(LSZ)作为模板药物，将载药样品置于pH值为7.40的模拟体液中，恒温37°C进行体外缓释实验。结果表明介孔棒状纳米磷灰石对BSA的负载量要大于对LSZ的负载量，这是由于沿c轴生长的棒状磷灰石，其a(b)晶面的面积比c晶面的面积大，导致了纳米粒子表面暴露的正电荷的数量相对于负电荷要多，使得在水溶液中呈负电性的BSA吸附量变大。此外随着羟基磷灰石比表面积和孔径的增大，对蛋白质的吸附量均增大。在药物释放阶段，介孔棒状纳米羟基磷灰石对BSA表现出很好的缓释性能，而LSZ则表现出了突释放现象。第四锶羟基磷灰石对BSA的负载量明显低于羟基磷灰石，这是由于锶的离子半径比钙离子半径略大，使其对BSA的静电吸引力变弱。在药物释放阶段，BSA从锶羟基磷灰石上的释放速率明显高于从羟基磷灰石上的释放速率。
[Abstract]:As a new drug carrier, nano-apatite with biocompatibility and bioactivity has been widely studied in the field of controlled drug release. In this paper, mesoporous nanocrystalline hydroxyapatite was synthesized by template-hydrothermal method, and rod-shaped strontium hydroxyapatite was synthesized by sol-gel method. Firstly, nanocrystalline strontium hydroxyapatite was synthesized by sol-gel method. The effect of aging time on the formation of strontium doped hydroxyapatite was investigated. It is found that the aging time is the key factor to determine the morphology of the sample. When the aging temperature is 60 掳C and the aging time is 48 h, the prepared strontium apatite has a rod-like structure with a diameter of about 30 nm and a length of 120 ~ 180 nm. Secondly, mesoporous nanocrystalline hydroxyapatite was synthesized by template-hydrothermal method. The effect of the amount of surfactant (F127) on the mesoporous structure of the sample was investigated. The nano-hydroxyapatite was characterized by XRDD-FT-SEMT-EDXTEMBET. The results show that the prepared hydroxyapatite is a mesoporous material with a rod-like structure and a high crystallinity. The particle diameter is about 25nm and the length is 75 ~ 125nm. When the dosage of F127 is 1.33 g, the specific surface area of rod-shaped apatite is 86.29m2g ~ (-1), the average pore volume is 0.27cm3g ~ (1), and the average pore size is 3.83 nm. Thirdly, the drug loading properties of mesoporous nanocrystalline apatite were studied. Bovine serum albumin (BSA) (BSA) and lysozyme (LSZ) were used as template drugs. The drug loaded samples were placed in simulated body fluid with pH value of 7.40, and sustained release experiments were carried out at 37 掳C at constant temperature. The results show that the amount of mesoporous nanocrystalline apatite loaded on BSA is larger than that on LSZ, which is due to the fact that the area of a (b) crystal plane is larger than that of c-crystal plane, because the rod-like apatite grows along c-axis. The amount of positive charge exposed on the surface of nanoparticles is higher than that of negative charge, which makes the adsorption capacity of BSA in aqueous solution larger. In addition, with the increase of specific surface area and pore size of hydroxyapatite, the adsorption capacity of protein increased. In the drug release phase, mesoporous nano-hydroxyapatite showed a good sustained release performance to BSA, while LSZ showed a sudden release phenomenon. The loading amount of the fourth strontium hydroxyapatite on BSA is obviously lower than that on the hydroxyapatite, which is due to the fact that the strontium ion radius is slightly larger than the calcium ion radius, which weakens its electrostatic attraction to BSA. The release rate of BSA from strontium hydroxyapatite was significantly higher than that from hydroxyapatite.
【学位授予单位】：天津大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R318.08

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