Poloxamer188~W/O乳液电纺卡铂聚L-乳酸纤维的制备和表征  

Prepareation and characterization of carboplatin loaded poly L-lactic acid fibrous films electrospun from Poloxamer188~-emulsified W/O emulsion

作　　者：崔银 张天 王浩 温梦 蔡东 CUI Yin;ZHANG Tian;WANG Hao;WEN Meng;CAI Dong(College of Pharmacy,Jinzhou Medical University,Jinzhou,121001,China;Center of Engineering and Technology for Drug Effection and Quality Evaluation,Jinzhou,121001,China)

机构地区：[1]锦州医科大学药学院,辽宁锦州121001 [2]药物作用与质量评价辽宁省工程技术中心,辽宁锦州121001

出　　处：《沈阳药科大学学报》2018年第10期831-839,共9页Journal of Shenyang Pharmaceutical University

基　　金：辽宁省自然科学基金资助项目(2014022041);国家自然科学基金资助项目(51102178);中国博士后基金资助项目(2014M561187)

摘　　要：目的制备一种能够缓释卡铂的局部化疗用纤维膜。方法药物的水溶液为水相,聚L-乳酸的二氯甲烷溶液为油相,Poloxamer188~为乳化剂,探头超声制备W/O乳液后静电纺丝将体系拉制成纤维。采用扫描电子显微镜观察纤维形态,采用广角-X射线衍射扫描法观察纤维表面有无药物结晶析出,采用差示热分析和傅立叶变换红外光谱评价药物在高分子纤维中的结合状态。碘-碘化钾络合显色法测定Poloxamer188~的释放,采用原子吸收分光光度法测定卡铂的释放,绘制释放曲线并回归。采用MTT法测试释放药物的抗He La细胞活性。结果扫描电子显微镜观察制备得到直径较为均一的纤维膜,乳液静电纺丝所得纤维直径大于均相溶液纺丝,乳液纺丝所得纤维表面有微小孔状结构。广角X-射线衍射结果表明纤维表面无药物结晶析出,差示热分析结果表明卡铂在纤维亦为非结晶状态存在,傅立叶变换红外光谱发现卡铂与纤维材料良好复合。各样品中卡铂突释明显,随着Poloxamer188~添加量的增多,其本身和卡铂均从纤维中的突释量逐渐增大,纤维中药物释放速率加快。当Poloxamer188~的复合量为10%、20%和30%时,缓释超过10 h。Poloxamer188~释放曲线复合Freundlich方程式,卡铂释放曲线符合0级释放动力学。结论 W/O乳液静电纺丝法能够制备得到对卡铂有缓释作用的抗He La细胞纤维膜。Objective To load carboplatin in poly L-lactic acid electrospun fibrous films and investigate the incorporation and release. Methods W/O emulsions were prepared first by using carboplatin water solution was used as internal phase,poly L-lactic acid dichloromethane solution as external phase,and Poloxamer188-of 10%,20%,30%,40%,50% mass ratio to poly L-lactic acid as emulsifier. Then fibers were prepared by electrospinning those emulsions and characterized by scanning electron microscopy for morphological characterization,by X-ray diffraction and differential thermal analysis to investigate the incorporating status. Atomic absorption spectrophotometry and complexing coloration spectrometry were used to detect the released carboplatin and Poloxamer188-for drawing the release curves of them,respectively.The antitumor activities of the carboplatin released from fibers against HeLa cells was evaluated by M TT method. Results M icro-scale fibers could be obtained after emulsion electrospinning. As the amount of complexed Poloxamer188-increased,the fibers diameter decreased and morphology was improved. There was no Poloxamer188-existing on the fibers surfaces,but seperated aggregates of Poloxamer188-may exist in the inner position of the fiber matrix. Poloxamer188-presented burst release. Carboplatin presented more than 10 h when the Poloxamer188-complexing amount was 10%,20%,30% and the release curve could be fitted as 0 order equation while release curves of Poloxamer188-fitted Frendlich ＇s equation. Released carboplatin reserved the anti-HeLa cell activity. Conclusion By W/O emuslion electrospinning with Poloxamer188-as emulsifier,carboplatin could be incorporated within the poly L-lactic acid fibrous films of acceptable morphology and desirable release behavior with anti HeLa cell activity.

关 键 词：静电纺丝 纤维 卡铂 泊洛沙姆 W/O乳液 聚L-乳酸 

分 类 号：R914[医药卫生—药物化学]