反相微乳液法制备聚乳酸生物微球及其载药研究

发布时间：2018-03-20 08:47

本文选题：聚乳酸　切入点：热致相分离　出处：《河北大学》2017年硕士论文　论文类型：学位论文

【摘要】：载药微球是一种新型药物制剂,可以通过调节和控制药物的释放速率实现长效缓释。本文采用反相微乳液结合相分离的方法制备具有多孔结构的微球,将其用作药物载体,研究其载药性能。本文主要分为两部分:第一部分:采用反相微乳液结合相分离的方法制备具有多孔结构的微球,探究了不同浓度、转速、聚乳酸(PLLA)分子量、相分离温度和溶剂对微球大小、结构和形貌的影响,并探究了不同结构的PLLA微球在药物缓释方面的应用。通过扫描电子显微镜(SEM)和Nano Measurer粒度分析软件对微球的形貌和粒径大小进行分析,结果显示,通过控制不同的反应条件可以制备出不同形貌和大小的PLLA多孔微球。二氧六环溶剂体系制备的D-PLLA微球表面是纳米珊瑚状‖的结构,内部有很多相分离产生的小孔(1-2μm)。由THF溶剂体系制备的T-PLLA微球具有纳米纤维状的结构(50-500nm)。使用两者的混合溶剂时微球的结构介于珊瑚状‖和纤维状之间。微球的细胞实验表明制备出的多孔微球具有良好的生物活性。微球的药物缓释实验显示D-PLLA微球和T-PLLA微球的载药量分别为7.2%和10.6%,体外缓释平稳,8h时累计释放量分别为41.2%和75.3%,是较好的药物载体。相对而言,T-PLLA微球的载药量相对较大,体外缓释时存在一定突释。第二部分:采用模拟体液(SBF)法,将第一部分制备的PLLA微球在1.5倍的SBF中浸泡不同时间,制备了聚乳酸/羟基磷灰石(PLLA/HA)复合微球,并对其进行载药实验。采用SEM表征了微球表面HA沉积层形貌、覆盖程度及HA晶粒晶型及尺寸。透射电镜(TEM)结果表明HA晶体呈薄片状;透射电镜能谱(TEM-EDS)测得HA层Ca/P原子比为1.40,接近真实比;TEM高分辨检测到HA的(110)和(002)晶面。X射线衍射(XRD)检测到HA层的(002),(211),(300)和(222)晶面处的特征衍射峰。FTIR图谱显示PLLA/HA复合微球既具有PLLA的特征吸收峰,同时也具有HA的特征吸收峰载药实验表明D-PLLA/HA载药微球的载药量为6.1%,体外缓释曲线较好,24h时累计释放89.7%,是一种较好的药物载体。T-PLLA/HA载药微球的载药量为8.1%,24h时累计释放93.9%,存在一定的突释。
[Abstract]:Drug-loaded microspheres are a new drug preparation, which can achieve long-term sustained release by regulating and controlling the drug release rate. In this paper, microspheres with porous structure were prepared by reverse microemulsion combined phase separation method and used as drug carriers. This paper mainly includes two parts: the first part: the microspheres with porous structure were prepared by reverse microemulsion combined phase separation method, and the molecular weight of PLLA was investigated at different concentration, rotational speed and polylactic acid (PLLA). Effects of phase separation temperature and solvent on the size, structure and morphology of microspheres, The application of PLLA microspheres with different structures in drug delivery was investigated. The morphology and particle size of PLLA microspheres were analyzed by scanning electron microscope (SEM) and Nano Measurer. PLLA porous microspheres with different morphology and size can be prepared by controlling different reaction conditions. The surface of D-PLLA microspheres prepared by dioxane solvent system is the structure of coral-like nanocrystalline. The T-PLLA microspheres prepared by THF solvent system have a nano-fibrous structure of 50-500 nm. The structure of the microspheres is between coral-like and fibrous when the mixed solvents of both are used. The structure of T-PLLA microspheres is between coral-like and fibrous. The structure of T-PLLA microspheres prepared by THF solvent system is between coral-like and fibrous, and the structure of T-PLLA microspheres is between coral-like and fibrous. Cell experiments showed that the porous microspheres had good bioactivity, and the drug release experiments showed that the drug loading of D-PLLA microspheres and T-PLLA microspheres were 7.2% and 10.6, respectively, and the accumulative release amounts of D-PLLA microspheres and T-PLLA microspheres were 41.2% and 10.6 respectively at 8 h of steady release in vitro. 75.3% is a good drug carrier. The drug load of T-PLLA microspheres is relatively large. In the second part, the PLLA microspheres prepared in the first part were soaked in 1.5 times of SBF for different time to prepare polylactic acid / hydroxyapatite / PLLA / HA composite microspheres. SEM was used to characterize the morphology of HA deposit layer on the surface of the microspheres, the coverage degree, the crystal structure and size of HA. The results of transmission electron microscopy (TEM) showed that the HA crystal was flaky. The Ca/P atomic ratio of HA layer measured by TEM energy dispersive electron microscopy (TEM) is 1.40, which is close to the real ratio. Tem high resolution detection of HA is 110) and the X ray diffraction (XRD)) of HA layer. X-ray diffraction (XRD) is used to detect the characteristic diffraction peak of PLLA/HA composite microsphere at the crystal plane of HA layer. Both have characteristic absorption peaks of PLLA, At the same time, the characteristic absorption peak drug loading experiment of HA also showed that D-PLLA / HA microspheres were loaded with 6.1and the accumulative release was 89.7at 24 hours after a better sustained release curve in vitro. It was a better drug carrier. T-PLLA-HA microspheres were loaded with 8.1and 24h cumulative release. 93.9, there is a certain sudden release.
【学位授予单位】：河北大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O633.14;TQ460.4

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