掺锶纳米介孔羟基磷灰石的合成、骨诱导性及作为药物递送载体的研究-有机化学专业论文.docxVIP

摘 摘 要 Abstract Abstract I I PAGE PAGE IV 摘要 随着世界人口老龄化的加剧，骨折成为影响公众健康的重大威胁，骨修复的需求量 也随之急剧增加。骨组织工程有望满足日益增加的骨修复需求。纳米级的磷酸钙生物材 料因其具有与自然骨的无机成分组成类似的特点，在骨组织修复中的应用研究引起广泛 关注。本论文设计合成了四种掺杂不同比例锶的 HAP 纳米颗粒，通过扫描电子显微镜、 透射电子显微镜、X-射线粉末衍射、动态光散射、比表面积测试仪等方法表征了其形貌、 尺寸以及组成；通过 MTT 法、溶血实验、诱导骨矿化等实验评价纳米颗粒的生物相容 性和骨诱导性；以纳米 HAP 为载体，采用紫外、荧光、红外、热重等检测方法，研究 了载体对阿伦磷酸钠的吸附、释放行为及释药机制。结果表明：所合成的 HAP 为棒状 的纳米介孔颗粒，长 80-100 nm，直径 20 nm，介孔孔径 2-3 nm；适量的锶掺入 HAP 纳 米颗粒可以提高其生物相容性和骨诱导性；纳米 HAP 载体通过静电吸附作用，将药物 阿仑膦酸钠吸附在载体表面，并以自由扩散的形式持续地从载体表面释放。所合成的四 种 HAP 纳米颗粒中，载体 CS3（20% Sr@HAP）纳米颗粒具有较好的载释药能力，载 药 48 h 后，载药量达到 0.85 mg (AL) / mg (载体)，体外模拟释药 15 d，累积释药量达到 76%，故 CS3 是一个理想的递送双磷酸类药物载体。鉴于棒状纳米介孔 HAP 载体本身 所具备的促进成骨细胞分化和矿化的能力，且载体所缓释的阿伦磷酸钠具有抑制破骨细 胞的骨吸收能力，我们推测，在治疗骨质疏松过程中，载体与药物可能起到协同治疗的 作用，在骨质疏松治疗方面具有潜在的应用前景。 关键词 纳米 HAP；阿伦磷酸钠；体外药物释放；药物递送；骨修复 Abstract With the speeding tendency of aging society, bone fracture becomes the serious disease to threaten the human life and the need for bone regeneration is increasing dramatically. Tissue engineering is promising to address this challenge. Recently, many efforts have been directed towards developing nanostructured calcium phosphate (CaP) biomaterials/scaffolds, which have the checmical/crystallographic similarities to inorganic components of bone. In our research, we designed and prepared four kinds of hydroxyapatites nanoparticles with different proportion strontium incorporation. The morphology, size distribution and composition of nanoparticles were measured using scanning electron microscope (SEM), X-ray diffractometer (XRD), dynamic light scattering (DLS) and specific surface area tester (BET). The biocompatibility, osteoconduction of the nanoparticles were evaluated by MTT, hemolytic and mineralization experiment. The behavior of drug absorbsion and releasing of alendronate (AL) were evaluated by UV-spectroscopy(UV), spectrofluorimetry(PL), fourier transform infrared spectrometry(FIR), thermogravimetric analysis(TGA) with HAP as drug delivery. The results indicated that morphology