硫酸多黏菌素B多囊脂质体的制备及抗菌活性研究  

Preparation and Antibacterial Activity of Polymyxin B Sulfate Multivesicular Liposomes

作　　者：卢宇欣 金锐 王娅雯 陈雪帆 LU Yuxin;JIN Rui;WANG Yawen;CHEN Xuefan(Green Pharmaceutical Collaborative Innovation Center,Zhejiang University of Technology,Hangzhou 310014,China)

机构地区：[1]浙江工业大学绿色制药协同创新中心,杭州310014

出　　处：《中国药学杂志》2025年第6期620-629,共10页Chinese Pharmaceutical Journal

基　　金：国家药典委员会药品标准制修订研究课题资助(2023Y002)。

摘　　要：目的 制备硫酸多黏菌素B多囊脂质体(polymyxin B sulfate multivesicular liposomes, PMB-MVLs),优化其处方并对其质量、稳定性、体外释放和体外抗菌活性进行考察。方法 采用复乳法制备PMB-MVLs,以包封率为指标,采用Box-Behnken效应面法对处方进行优化;采用高效液相色谱法对PMB-MVLs中PMB进行定量分析;对其理化性质、药物体外释放行为、体外抗菌活性和制剂安全性进行考察。结果 采用最优处方所制的PMB-MVLs外观呈无数个非同心囊泡堆积而成的球形,大小较均匀,包封率为(69.521±1.531)%,平均粒径为(5.84±1.42)μm,平均Zeta电位为(-26.77±0.55)mV,其在4℃下储存1个月稳定性良好;PMB-MVLs在体外持续释放达72 h,无突释效应;体外抗菌实验结果显示,相较于PMB溶液,PMB-MVLs对E.coli和P.aeruginosa细菌具有更好的抗菌效果,并且在其抗菌活性范围内无溶血风险。结论 成功制得具有缓释作用的PMB-MVLs,其粒径分布均匀、包封率高,具有增强的抗菌活性。OBJECTIVE To prepare polymyxin B sulfate multivesicular liposomes(PMB-MVLs),optimize their formulation,and their quality,stability,release and investigate their antibacterial activity in vitro.METHODS The PMB-MVLs were prepared by the double-emulsion method.The response surface method of Box-Behnken design was used to optimize the initial prescription.High performance liquid chromatography method was established to quantitatively analyze PMB in PMB-MVLs.The physicochemical properties,the in vitro drug release behavior,in vitro antimicrobial activity and formulation safety of PMB-MVLs were investigated.RESULTS The appearance of PMB-MVLs prepared by optimal prescription were non-concentric spherical vesicles with uniform size.The encapsulation efficiency of PMB-MVLs were(69.521±1.531)%.The average particle size was(5.84±1.42)μm,and the average Zeta potential was(-26.77±0.55)mV.The PMB-MVLs showed good stability when stored at 4℃for one month.The results showed that PMB-MVLs were released continuously for 72 h in vitro,and there was no sudden release effect.The in vitro antibacterial activities of PMB-MVLs on E.coli and P.aeruginosa were significantly stronger than those of the free PMB.And PMB-MVLs has no risk of hemolysis within its range of antimicrobial activity.CONCLUSION The slow-release PMB-MVLs are successfully prepared with uniform particle size,high encapsulation efficiency,and enhanced antibacterial activity.

关 键 词：硫酸多黏菌素B 多囊脂质体 复乳法 BOX-BEHNKEN设计 体外抗菌 

分 类 号：R944[医药卫生—药剂学]