两性霉素B脂质体-微球的制备及工艺优化  

Preparation and process optimization of amphotericin B liposome-encapsulated microspheres

作　　者：徐伟 于洋[1] 陈逸鹏 余昆胜 李翀[1] 陈章宝[1] Xu Wei;Yu Yang;Chen Yi-peng;Yu Kun-sheng;Li Chong;Chen Zhang-bao(College of Pharmaceutical Sciences,Southwest University,Chongqing 400715)

机构地区：[1]西南大学药学院,重庆400715

出　　处：《中国抗生素杂志》2018年第7期893-900,共8页Chinese Journal of Antibiotics

基　　金：中央高校基本科研业务费专项资金项目(No.XDJK2016C075);重庆市社会民生科技创新专项(No.cstc2015shmszx00003)

摘　　要：目的应用Box-Behnken响应面分析法优化两性霉素B脂质体-微球的制备条件。方法采用乳化-相分离法制备包载两性霉素B脂质体的海藻酸钠微球,通过单因素实验确定显著影响微球成球性的因素,利用Box-Behnken响应面分析法考察氯化钙浓度、司盘80用量及搅拌速度对微球粒径、跨距、包封率、1h释放量及72h释放量的影响,筛选最佳制备工艺,并进行体外抑菌试验。结果最佳制备工艺条件为氯化钙浓度41%,司盘80用量4.3%,搅拌速度678r/min。此优化条件下,制得的两性霉素B脂质体-微球平均粒径为8.0μm,药物包封率大于80%,体外抑菌试验结果显示载药微球具有较好的抑菌能力。结论 BoxBehnken响应面分析法可有效平衡各因素之间的相互影响,适用于两性霉素B脂质体-微球的制备工艺筛选。Objective A three-factor Box-Behnken experimental design was used to optimize the formulation of amphotericin B liposome-encapsulated microspheres. Methods Amphotericin B liposome-encapsulated microspheres were prepared using an emulsification phase-separation method. Based on results of the single factor experiments, the effects of the CaCl2 concentration, the Span 80 concentration, and the rotation speed on the particle size, span, entrapment efficiency, and release behaviors were studied using a Box-Behnken response surface design. Results Using this developed model, the optimal conditions included that the CaC12 concentration was 41%, the Span 80 concentration was 4.3%, and the rotation speed was 678r/min. Under the optimized conditions, the average size of microspheres was 8.0μm, and the encapsulation efficiency was over 80%. In vitro antifungal susceptibility tests of amphotericin B microspheres demonstrated their ability to inhibit the growth of Cryptococcus neoformans. Conclusion The Box-Behnken design combined with the response surface analysis could effectively balance the interactions among various factors, and thus is suitable for optimizing the microsphere preparation process.

关 键 词：两性霉素B脂质体 肺靶向微球 Box-Behnken响应面分析法 

分 类 号：I978.15[文学]