丝素改性PLGA载阿奇霉素微球制备及体外释放研究

发布时间：2018-04-11 19:38

本文选题：PLGA + 阿奇霉素　；参考：《天津医科大学》2017年硕士论文

【摘要】：目的:牙周炎是一种发病率高且常见的慢性病,对牙齿支持组织有着广泛的影响,临床表现为牙龈的炎症和出血、牙周袋的形成、牙槽骨吸收,和牙齿的松动、移位,是成年人失牙的主要原因。炎症反应是免疫细胞、免疫分子、炎症介质共同参与的结果。在牙周微生物和宿主的相互作用中,宿主的反应决定了牙周炎的进程。炎症微环境是造成牙周组织丧失和再生困难的主要原因,寻找能够调控牙周炎症微环境的方法是牙周组织再生的关键。阿奇霉素作为临床上治疗牙周炎常用的大环内酯类抗生素,对炎性细胞因子具有下调作用,对破骨细胞的成熟分化具有抑制作用,临床上直接应用于牙周炎治疗的有效性已经得到了充分的肯定,但是长期使用易产生耐药性,易发生不良反应;口腔环境的复杂性及其特殊的解剖结构,使局部用药作用时间受限,有必要研发一种局部药物缓释体系促进阿奇霉素在牙周炎治疗中的应用。聚乳酸羟基乙酸共聚物(PLGA)具有良好的生物相容性和生物可降解性,在药物递送系统和组织修复领域得到了深入研究。但由于PLGA表面具备疏水性,不易吸附黏膜,利用天然高分子材料丝素蛋白修饰载阿奇霉素PLGA微球,不仅可以改善表面亲疏水性,增强对粘膜的亲附力,也可中和PLGA降解的酸性产物,维持口腔正常生理PH值,同时使阿奇霉素缓慢释放,从而达到治疗牙周炎的目的。方法:1.制备载阿奇霉素PLGA微球并进行体外释药性检测采用乳液-溶剂挥发法制备载阿奇霉素的PLGA微球,通过扫描电镜及透射电镜观察其表面形貌及结构,优化实验条件,获得合理的载药量和包封率。2.聚(丙烯胺盐酸盐)(PAH)及丝素蛋白对载阿奇霉素PLGA微球的改性修饰并进行体外释药性检测以层层自组装法将PAH及丝素蛋白沉积在载阿奇霉素PLGA微球表面,通过Zeta电位和微球表面形态变化证实壳层材料的成功沉积。计算壳层材料修饰后的载阿奇霉素PLGA微球的载药量及包封率;绘制壳层材料修饰后的载阿奇霉素PLGA微球的体外累积释药曲线。结果:1.在扫描电子显微镜下可见,不同搅拌速度制备的微球表面形态、粒径大小均存在显著性差异。搅拌速度越快(8000rpm),微球粒径越小,表面形态较光滑;搅拌速度越慢(800rpm)微球粒径越大,表面形态较粗糙呈点状凹坑样。通过测定不同质量比的载阿奇霉素PLGA微球的药物释放,发现初始释药阶段呈明显的“突释”,后续的释放过程比较平稳,随着PLGA的降解,阿奇霉素可以持续缓慢释放。2.在扫描电镜下观察经修饰后的载阿奇霉素PLGA微球,可以发现微球表面被覆有壳层材料,微球周围可见析出的丝络样修饰材料,经Zeta电位检测证实了PAH及丝素蛋白的成功沉积。通过测定修饰后载阿奇霉素的PLGA微球的药物释放,可以发现经修饰后载药微球中的阿奇霉素释放量明显减少,阿奇霉素释放速率得到调控。结论:1、以PLGA为载体材料阿奇霉素为加载药物的药物缓释体系的搅拌速率不同制备的载药微球形态及性质不同,可根据所需药物缓释体系进行制备方式的设计。2、提高投药比例,载药微球的载药量及包封率上升,当投药量达到峰值时,包封率明显下降。3、经过聚(丙烯胺盐酸盐)及丝素的成功改性,载药微球的药物释放速率可以被调控。4、本实验为阿奇霉素的缓慢释放提供了体外研究证据,从而为后续体内实验奠定了基础。
[Abstract]:Objective: Periodontitis is a chronic disease with high incidence and common, the teeth support has a broad impact, the clinical manifestations of gingival inflammation and bleeding, periodontal pocket formation, alveolar bone resorption, and teeth loosening, displacement, is a major cause of tooth loss in adults. The inflammatory reaction is immune cells and immune molecules and inflammatory mediators involved in the interaction. In periodontal microorganisms and the host, the host reaction determines the periodontitis process. The inflammatory microenvironment is mainly caused by the loss and difficult regeneration of periodontal tissues, find the method can control inflammation microenvironment is critical for periodontal tissue regeneration azithromycin. As the clinical treatment of periodontitis of macrolide antibiotics commonly used, with a reduced role of inflammatory cytokines, inhibits the differentiation of osteoclasts, directly applied to clinical periodontal The effectiveness of anti-inflammatory treatment has been fully confirmed, but the long-term use is easy to produce drug resistance, prone to adverse reactions; the complexity of oral environment and its special anatomical structure, so that the local drug action time is limited, it is necessary to develop a drug delivery system promotes the application of azithromycin in the treatment of periodontitis. PLGA the copolymer (PLGA) has good compatibility and biodegradability of the organisms, is being studied in the field of drug delivery systems and tissue repair. But with the hydrophobic PLGA surface, is not easy to absorb the mucosa, natural polymer modified silk fibroin microspheres containing azithromycin PLGA, can not only improve the surface hydrophobicity, enhancement of mucous membrane the attachment force can neutralize PLGA degradation of acidic products, maintain normal oral physiological pH, and the slow release to azithromycin. The treatment of periodontitis. Methods: 1. preparation containing azithromycin PLGA microspheres and PLGA microspheres in vitro release test preparation containing azithromycin by emulsion solvent evaporation method, observe the surface morphology and structure by scanning electron microscopy and transmission electron microscopy, optimizing the experimental conditions, reasonable loading and encapsulation rate of.2. poly (propylene amine hydrochloride) (PAH) and silk fibroin on PLGA microspheres containing azithromycin modification and drug release in vitro detection by layer self-assembly method and PAH silk fibroin deposited on the surface of PLGA microspheres containing azithromycin, the Zeta potential and the surface morphology of the microspheres confirmed the successful deposition changes of shell materials. Calculation of shell materials after modification the PLGA containing azithromycin microspheres loading and encapsulation rate; drawing shell materials of modified PLGA containing azithromycin microspheres in vitro cumulative drug release curve. Results: 1. in scanning electron microscopy Microscopically, different stirring speed, the surface morphology of microspheres prepared by particle size were significantly different. The faster stirring speed (8000rpm), the smaller particle size of microspheres, the surface morphology is smooth; the stirring speed is slower (800rpm) microspheres with larger particle size, surface morphology of coarse punctate pits. The release of PLGA microspheres containing azithromycin drug determination of different mass ratio, it is found that the initial release stage showed a burst release and subsequent release process is relatively stable, with the degradation of PLGA, azithromycin sustained release of.2. can be observed by modified PLGA microspheres containing azithromycin can be found under the scanning electron microscope, surface coated microspheres shell material, microspheres precipitated wire winding around like modified materials by Zeta potentiometric detection confirmed the successful deposition of PAH and silk fibroin. PLGA microspheres modified by determination of drug release carrier of azithromycin Can be found, azithromycin modified microspheres release in significantly reduced, the release rate of azithromycin control. Conclusion: 1. Using PLGA as carrier materials for drug delivery system of azithromycin drug loaded the stirring rate of different preparation of microspheres morphology and properties of different, according to the required drug delivery system the design of.2 preparation methods, improve the dosage proportion of microspheres loading and encapsulation rate increased when the dosage reached the peak, the encapsulation rate was significantly decreased after.3, poly (allylamine hydrochloride) and silk fibroin modified release rate can be regulated.4 drug loaded microspheres this experiment provides evidence for the slow release of azithromycin in vitro, which lays the foundation for the subsequent in vivo experiments.

【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R781.4

【参考文献】