【作者】 张丹；

【导师】 吴小红；

【作者基本信息】 重庆医科大学 ， 口腔医学（专业学位）， 2020， 硕士

【摘要】 在生物医学研究中,静电纺材料得到越来越广泛的应用,但即使将药物负载在成骨材料中仍存在明显的突释现象和难以达到长期控释。药物突释易造成前期药物浓度过高产生药物毒性,后期则因药物浓度过低丧失药效性,不利于骨的形成。微球/贮库作为一种局部药物传递装置,可以有效地减少药物突释和延长药物释放时间,且可通过改变微球/贮库中的内容物来调控其药物释放行为。本实验将聚乳酸-羟基乙酸共聚物(Poly(lactic-co-glycolic acid),PLGA)、聚乙二醇(Polyethylene glycol,PEG)、柚皮苷(Naringin,Ng)与氯仿混合并经磁力搅拌后配成静电纺溶液,采用静电喷雾技术,调节电喷雾参数以制备出不同大小的载柚皮苷电喷微球,用扫描电子显微镜(Scanning electron microscopy,SEM)和偏振光显微镜(Polarized light microscope,Polscope)观察其大小和形态,并测定其表征和释药性能;再将不同大小的微球分散于乙酸异丁酸蔗糖酯(Sucrose acetate isobutyrate,SAIB)贮库中,制备微球/SAIB复合型原位贮库,测定其释药性能和孔隙率。结果显示:利用电喷雾技术,在温度和湿度范围分别为22℃~23℃和30~31%RH时,采用流速(0.030 mm/min)、收集距离(20 cm)和外加电压(22 kV)制备了小的电喷微球,采用流速(0.120 mm/min)、收集距离(15 cm)和外加电压(18 kV)制备了大的电喷微球,且大小微球均显示出光滑的表面,并具有良好的单分散性和亲水性。将电喷微球加入SAIB贮库后,小微球组第1天的药物释放率从68.79%降为3.30%,大微球组的则从63.20%降为0.00%;在92天的释药过程中,大微球/SAIB贮库的药物释放率一直低于小微球/SAIB贮库。以上结果表明,利用PLGA/PEG通过电喷雾技术调整电纺参数可制备出大小不同的电喷微球;电喷微球/SAIB复合型原位贮库体现出良好的药物初期控释和长期缓释能力,其药物释放行为可以通过改变电喷微球的大小来调整。更多还原

【Abstract】 In biomedical research,electrospinning materials have been used more and more widely,but even when drugs are loaded in osteogenic materials,there is still an obvious drug burst release and it is difficult to achieve long-term controlled release.Drug burst release tends to cause high drug concentration in the early stage to produce drug toxicity,while in the later period,the pesticide effect is lost due to low drug concentration,which is not conducive to bone formation.As a local drug delivery device,the microsphere / depot can effectively reduce the drug burst release and prolong the drug release time,and its drug release behavior can be regulated and controlled by changing the contents of the depot.In this study,the polymer solution made by PLGA,PEG and Ng dissolved in chloroform were mixed and magnetically stirred,and different size of naringin-loaded microspheres were produced by adjusting the electrospinning parameters.The size and morphology of electrospinning microspheres were observed with SEM and POLSCOPE,and the effect of particle size on physicochemical properties and drug release properties were measured.The results showed that different size of electrospinning microspheres were produced.The temperature and humidity range were 22℃ ~ 23℃ and 30 ~ 31% RH,and small electrospinning microspheres were produced with a slower flow rate of 0.030 mm/min,a voltage of 22 kV and a working distance of 20 cm,while the parameters for the large electrospun microspheres were 0.120 mm/min,18 kV and 15 cm.Both the small and large microspheres showed good monodispersity and smooth surface.After adding them into the SAIB depots,the drug release rate of the small microsphere group decreased from 68.79% to 3.30% on the first day,and the large microsphere group decreased from 63.20% to 0.00% on the first day.During the 92 days release process,the drug release rate of large microspheres / SAIB depot has been always lower than that of small microspheres / SAIB depot.These results demonstrated that different size of drug-loaded electrospinning microspheres could be fabricated with PLGA / PEG by regulated the electrospinning parameters.The microspheres / SAIB depots exhibited good initial controlled release and long-term sustained release capabilities.Different sizes of electrospinning microspheres showed different characteristics and the drug release behavior can be adjusted by changing the size of the microspheres.更多还原