纳米类水滑石的可控制备、药物传递及抗肿瘤性能

发布时间：2018-03-21 23:30

本文选题：类水滑石　切入点：多孔支架　出处：《上海师范大学》2015年硕士论文　论文类型：学位论文

【摘要】：化疗药物甲氨蝶呤(MTX)在体内不能够长时间维持有效药物浓度,显著降低了对骨肿瘤的治疗效果。解决上述问题的有效途径是构建药物传递系统,使抗肿瘤药物能够在病灶部位进行局部、持续、缓慢地释放。类水滑石(LDHs)具有良好的生物相容性、低毒性和药物传递性能,被广泛地用于负载药物。所以可以通过将MTX负载在类水滑石上,作为另一种治疗骨肉瘤的方法。本文通过共沉淀法合成碳酸根型镁铝类水滑石(LDHs-C),通过焙烧还原法插入不同功能性阴离子,分别制备了硝酸根型、硅酸根型和磷酸根型镁铝类水滑石(LDHs-N、LDH-Si和LDH-P),借助SEM、TEM、XRD、FTIR、BET与ICP等分析手段表征类水滑石的表面形貌与物相结构。四种类水滑石为层状结构,具有六方片状形貌,具有较大的比表面积(LDHs-C为107.407 m2/g,LDHs-N为205.22m2/g、LDH-Si为153.538 m2/g和LDH-P为34.634 m2/g),由于类水滑石纳米片之间堆积产生了介孔结构。不同的层间阴离子对类水滑石的稳定性有一定影响,稳定性顺序为LDH-SiLDH-PLDH-CLDH-N。不同类水滑石在去离子水中具有不同溶解度,可释放出Mg2+和所对应的阴离子。采用人骨髓间充质干细胞(h BMSCs)体外培养实验初步探索了四种类水滑石的生物相容性能和骨诱导性;通过测定样品中MTX的浓度,确定四种类水滑石的药物负载和释放性能;通过观察人骨肉瘤细胞Saos-2接种于负载不同量MTX的LDHs上的生长情况,探索四种类水滑石的抗骨肉瘤能力。四种类水滑石均为生物安全材料,表现出了良好的生物相容性,优于Hap的MTX药物负载率、药物缓释效果和抗骨肉瘤性能。LDHs-Si表现出了较好的骨诱导能力可以促进成骨基因的表达。为了研究类水滑石材料的临床可行性,通过浸渍-提拉和水热转化法构建了类水滑石/壳聚糖/碳纤维多孔支架(LDHs/CS/CFs),并通过SEM、TEM、XRD、FTIR、XPS与TG-DTA等分析手段对其进行表征。合成LDHs/CS/CFs的最佳碱性条件为p H=10,此时多孔支架复合材料具有最佳的形貌,LDHs/CS在碳纤维毡上均匀涂覆,LDHs纳米片在碳纤维毡上垂直生长。通过浸泡SBF溶液,初步探索其体外活性,结果表明,构建的LDHs/CS/CFs具有较好的体外活性,可以促进片状类骨型磷灰石的形成。采用人骨髓间充质干细胞(h BMSCs)体外培养实验初步探索了其生物相容性能,表明LDHs/CS/CFs具有较好的生物相容性,h BMSCs细胞在其表面具有较强的生长能力与良好的铺展性。
[Abstract]:The chemotherapeutic drug methotrexate (MTX) can not maintain the effective drug concentration for a long time in vivo, which significantly reduces the therapeutic effect on bone tumor. The effective way to solve the above problem is to construct a drug delivery system. So that antitumor drugs can be locally, continuously, slowly released at the site of the lesion. The hydrotalcite-like LDHs have good biocompatibility, low toxicity and drug delivery. Is widely used to load drugs. So you can load MTX on hydrotalcite-like rocks, As another method of treatment for osteosarcoma, LDHs-Con was synthesized by coprecipitation method. Different functional anions were inserted into the hydroxides by roasting reduction method, and nitrate type was prepared respectively. The surface morphology and phase structure of hydrotalcite-like hydrotalcite are characterized by SEMTEMT-XRDX FTIRBET and ICP. The four kinds of hydrotalcite are layered and have hexagonal flake morphology. LDHs-C = 107.407 m ~ (2) / g ~ (-1) LDHs-N = 205.22 m ~ 2 / g ~ (-1) LDH-Si = 153.538 m ~ (2 / g) and LDH-P = 34.634 m ~ (2 / g) 路g ~ (-1). Because of the accumulation of hydrotalcite-like nanocrystals, mesoporous structure was formed. Different interlayer anions have some influence on the stability of hydrotalcite. The order of stability is LDH-SiLDH-PLDH-CLDH-N.The different hydrotalcite have different solubility in deionized water. The biocompatibility and bone inductivity of four kinds of hydrotalcite were preliminarily investigated by using human bone marrow mesenchymal stem cells (hBMSCs) in vitro, and the concentration of MTX in the samples was determined. To determine the drug loading and release properties of four kinds of hydrotalcite, to observe the growth of human osteosarcoma cell line Saos-2 inoculated on LDHs loaded with different amount of MTX, To explore the ability of anti-osteosarcoma of four kinds of hydrotalcite. The four kinds of hydrotalcite are biosafety materials, which show good biocompatibility and are superior to the drug loading rate of MTX of Hap. In order to study the clinical feasibility of hydrotalcite-like materials, drug slow-release and anti-osteosarcoma .LDHs-Si showed good osteoinductive ability to promote the expression of osteogenic gene. The hydrotalcite / chitosan / carbon fiber porous scaffolds LDHs / CS / CFS / CFS / CFS were constructed by impregnation-Czochralski and hydrothermal transformation. The LDHs / CS / CFS / CFS were characterized by SEMTEMT-XRDX FTIR XPS and TG-DTA. The optimum basic conditions for the synthesis of LDHs/CS/CFs were pH10, and the porous scaffolds were obtained. The composite material has the best morphology and the LDHs / CS is evenly coated on the carbon fiber felt and grown vertically on the carbon fiber felt. By soaking the SBF solution, The results showed that the constructed LDHs/CS/CFs had good activity in vitro and could promote the formation of bone like apatite. The biocompatibility of the constructed LDHs/CS/CFs was preliminarily explored by using human bone marrow mesenchymal stem cells (BMSCs) in vitro culture. The results showed that LDHs/CS/CFs had good biocompatibility on the surface of BMSCs cells and had strong growth ability and good spreading ability.
【学位授予单位】：上海师范大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：TQ460.1;TB383.1

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