【作者】 吴海燕；

【导师】 谢瑞娟；

【作者基本信息】 苏州大学 ， 纺织材料与纺织品设计， 2008， 硕士

【摘要】 本文以丝素蛋白(SF)为载体,以地塞米松磷酸钠(DSP)为药物模型,采用W/O/W型复乳法,制备丝素微球和丝素载药微球。用扫描电镜观察微球的表面形态,使用激光粒度仪测量粒径大小及分布,采用X-射线衍射法,红外光谱法和DTA差热分析法研究微球的结构。采用MTT法检测丝素微球的细胞毒性,采用药物体外释放法测定微球的释药性能。探讨了乳化剂比例、有机溶剂种类、有机溶剂与丝素比例、丝素浓度、地塞米松磷酸钠与丝素比例对微球制备及其性能的影响。实验结果表明:微球外观形态近似球型,丝素微球的平均粒径在0.56μm～56.52μm之间,随着乳化剂比例的增加,丝素微球的平径粒径逐渐减小,尤其乳化剂比例大于3%时,减少明显;随着丝素浓度的增加,丝素微球的粒径增加,特别是当丝素浓度大于6%时尤为明显;当有机溶剂与丝素比例由1:1增加到2:1时,丝素微球粒径减小明显,但当有机溶剂与丝素比例大于2:1时,微球粒径变化不明显。丝素载药微球的平均粒径在6.53μm～66.27μm之间。纯丝素的结构主要为无定型。使用不同的有机溶剂、不同的有机溶剂与丝素比例、不同的丝素浓度制得的丝素微球和丝素载药微球,其结构同纯丝素相比均发生了明显的变化,聚集态结构主要为SilkⅠ和SilkⅡ结构,分子构象主要为β-折叠。使用三种不同的有机溶剂制得的丝素微球其细胞毒性均为0级,即无细胞毒性。不同工艺条件下制得丝素载药微球的平均载药率在2.31%～9.01%之间,平均包埋率在31.28%～99.07%之间。微球的释放情况:1h的释药率均在50%左右,当DSP/SF比例在1:20～1:40之间、有机溶剂与丝素比例在4:1～6:1之间和丝素浓度在3%～6%范围内,有一定的缓释效果,尤其当DSP/SF比例在1:20～1:40范围内和有机溶剂与丝素比例为5:1～6:1时,4h开始释药速度减慢明显,96h释放了总药量的85%左右。其他工艺条件下制得的丝素载药微球突释现象较明显。更多还原

【Abstract】 A w/o/w double emulsion method was developed to prepare silk fibroin microspheres using silk fibroin (SF) as vehicle, dexamethasone sodium phosphate (DSP) as drug model. The surface shape was observed by SEM, the particle diameter’s size and distribution were observed by Laster particle sizer. The structure was studied by X-ray, FTIR and DTA. The cytotoxicity was assessed by MTT assay. The properties of drug release was assessed by in vitro release method. The effect on the preparation of SF microspheres and properties were investigated by the ratio of emulsifier, the variety of organic solvent, the organic solvent :SF ratio, the concentration of SF, the DSP : SF ratio.The results showed that the microsperes approximatively spherical. The SF microspheres’average size was between 0.56～56.52μm, and the particle sizes decreased with the ratio of emulsifier increased, there was an obviously decrease when the ratio above 3%. The particle size of SF microspheres increased with the concentration of SF increased, especially above 6%. The particle size of SF microspheres decreased obviously when the organic solvent : SF ratio added from 1:1 to 2:1, but there was no obvious change above 2:1. The drug-loading microspheres’average size was between 6.53～66.27μm. The structure of pure silk fibroin was mainly amorphism. The structure of SF microspheres and drug-loading microspheres prepared by different organic solvent, different organic solvent :SF ratio, different concentration of SF had an obviously change compared to pure SF, the state of aggregation was mainly silkⅠand silkⅡand conformation wasβ-sheet. The cytotoxicity rank of SF microspheres prepared by the three different organic solvent were 0, this showed non-poisonous. The average drug-loading efficiency was between 2.31%～9.01% and the average encapsulation efficiency was between 31.28%～99.07%. Drug release of microspheres:the release rate was about 50% for 1h, there had a slow release effect when the DSP : SF ratio was between 1:20～1:40, the organic solvent : SF ratio was between 4: 1～6:1 and the concentration of SF was between 3%～6%, especially the DSP :SF ratio was between 1:20～1:40 and the organic solvent : SF ratio was 5: 1～6:1. After 4h had passed, the release rate obviously decreased, and the quantity of the released drug was about 85% of the total. The SF drug-loading microspheres prepared under other technologies had an obvious suddenly release.更多还原