离子交换型栓塞微球及其载平阳霉素的制备与性质研究

Preparation and property study of ion-exchange embolic microspheres for delivering pingyangmycin

目的:研究离子交换型聚乙烯醇-丙烯酸微球(PVA-AA-Ms)的制备方法及其理化性质和载药性能。方法:采用反相悬浮聚合法制备PVA-AA-Ms,以光学显微镜观察微球的形态、测定粒径大小,以红外光谱法考察微球聚合物的结构,以化学滴定法测定离子交换官能团羧基的含量,以物性测定仪测量微球的抗压弹性。采用平阳霉素为模型药物,制备PVA-AA-Ms载药微球,以紫外分光光度法测定微球的载药量、包封率和体外累积释放百分数。结果:所制备的PVA-AA-Ms圆整,粒径范围为150～1000μm,平均粒径为500μm。红外光谱确证了聚乙烯醇与丙烯酸的聚合交联,微球的羧基含量为8.905mmol/g,微球具有较好的抗压弹性。微球载药量为30g/L,包封率为99.4%,药物在磷酸盐缓冲液(PBS)中缓慢释放,24h累积释放率为88.3%,药物累积释放50%的时间(t50)为2.19h。结论:PVA-AA-Ms的理化性质达到了栓塞治疗的要求,并且由于其羧基含量较高,具有交换载入阳离子药物(如含氨基的药物)的能力,可望为栓塞化疗提供一种新型的药物输送系统。

Objective： To develop and study the properties of ion-exchange polyvinyl alcohol-acrylic acid mierospheres （PVA-AA-Ms） for embolization. Methods： The PVA-AA-Ms were produced by the method of inverse suspension polymerization. The morphology and particle size were determined by optical microscope; FT-IR was used to investigate the special functional groups of PVA-AA-Ms; the carboxyl content of PVA-AA-Ms was measured by chemical titration; the compression elasticity was examined by texture analyzer （TA-plus）. Pingyangmycin （bleomycin A5 ） was used as model drug to prepare drugloaded PVA-AA-Ms. Drug loading and entrapment efficiency were measured through UV-spectrophotometer; in vitro drug release characteristic was detected by constant temperature vibration dialysis assay. Results： The PVA-AA-Ms were round and integrated. The average diameter of PVA-AA-Ms was 500 μm with a range of 150 - 1 000 μm. The carboxyl vibration was demonstrated by FT-IR and the content of earboxyl was 8. 905 mmol/g. PVA-AA-Ms were mechanically stable with appropriate elasticity. Drug loading and entrapment efficiency were 30 g/L and 99.4% , respectively. The drug release rate was slow in phosphate buffer solution （PBS） , 88.3% of the drug was released after 24 h and the t50 was 2.19 h. Conclusion： PVA-AA-Ms prepared in this study were supposed to be suitable for clinical embolization according to the physicochemieal properties. The high carboxyl content of PVA-AA-Ms which allowed them to load cationic drugs （e. g. , drug with amino group） through ion-exchange mechanism brought broad prospects for combination of embolization and chemotherapy.