载表阿霉素聚乳酸微球的制备及性质研究

Preparation and Characterization of Polylactide Microspheres Containing Epirubicin

表阿霉素是广谱的抗肿瘤药物,为了减少给药量,降低药物的毒副作用,并达到缓慢释放的目的,本研究以Span-80和Tween-80复合乳化剂为初乳乳化剂,以聚乙烯醇水溶液为复乳乳化剂,采用复乳-溶剂挥发法制备了聚乳酸载药微球,并分别用激光粒度分析仪,光学显微镜,透射电子显微镜,扫描电子显微镜以及激光共聚焦显微镜对微球微观形态进行了表征.通过优化实验,所得载表阿霉素聚乳酸微球粒径2-5μm,载药率最高可达到4.39%,包封率达37.2%,72h体外累积释放量为34.9%,具有明显的缓释效果.本研究制备了表阿霉素缓释新剂型,为进一步的动物实验、临床实验和临床应用提供了有价值的参考数据,有很好的应用前景.

Epirubicin is an anthracycline antibiotic and antitumor epimer of doxorubicin that has been used to treat a wide range of cancers. Polylactic acid （PLA） microspheres containing epirubiein hydrochloride were prepared with double emulsion-solvent evaporation technique in order to reduce the side effect and the dose of drug. The complex of sorbitan monooleate （SpawS0） and sorbitan polyoxyethylene monooleate （Tween-80） （1 ： 5 by vol. ） was used as emulsifier of the primary emulsion. The second emulsion was emulsified with Poly（vinyl alcohol） （PVA） as surfactant. We investigated the properties of the microspheres about size, morphology, drug loading, encapsulation efficiency and drug release in vitro, by means of dynamac light scattering, optical microscope, transmission electron microscopy （TEM） ,scanning electron microscopy （SEM） and confocal laser scanning microscope（CLSM） and so on. The results of optimization showed that the microsphere size of about 2-5μm was the optimal. The drug loading and encapsulation efficiency reached 4.39 % and 37.2 %, respectively. The epirubicin release from the PLA microspheres was sustainable and slow, cumulative release of epirubicin in 72 h was 34. 9% in vitro. To some extent,this study＇about PLA microspheres containing epirubiein has a potential application in drug delivery system and valuable references for the relative experiments in vivo and in clinic.