硫酸阿米卡星多囊脂质体的制备及评价  

Preparation and evaluation of the amikacin sulfate multivesicular liposomes

作　　者：张淼 邓盛齐[1] 张亦斌[1] 郑林[1] 陶静[1] Zhang Miao;Deng Sheng-qi;Zhang Yi-bin;Zheng Lin;Tao Jing(Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province,Sichuan Industrial Institute of Antibiotics,School of Pharmacy,Chengdu University,Chengdu 610106)

机构地区：[1]成都大学,药学院,四川抗菌素工业研究所,抗生素研究与再评价四川省重点实验室,成都610106

出　　处：《中国抗生素杂志》2023年第1期69-78,共10页Chinese Journal of Antibiotics

摘　　要：目的制备硫酸阿米卡星多囊脂质体(amikacin sulfate multivesicular liposomes,AMK-MVLs),对其进行质量评价,并考察了其体外抗菌活性。方法采用复乳法制备AMK-MVLs混悬液Ⅰ,Box-Behnken效应面法优化筛选最佳处方,采用生理盐水洗涤后调整药物浓度得AMK-MVLs混悬液。采用光学显微镜、激光粒度仪、差示扫描量热(differential scanning calorimeter,DSC)考察制剂的理化性质,采用透析法考察其体外释放规律,通过微量稀释法初步考察其体外抗菌活性。结果优化得到AMK-MVLs混悬液Ⅰ的最佳处方为:大豆磷脂与胆固醇质量比为1.91:1,三油酸甘油酯用量为1.02%,PVA用量为0.62%。AMK-MVLs呈堆叠有无数囊泡的非同心球状,AMK-MVLs混悬液包封率(87.12±1.55)%,平均粒径为11.93μm。DSC结果表明,AMK以无定型状态存在于脂质体内。体外释放结果显示AMK-MVLs混悬液在72 h时释药约80%。体外溶血实验表明,AMK-MVLs脂质体粒子浓度低于400μg/mL时无溶血风险。体外抗菌实验结果显示,相较于AMK溶液,AMK-MVLs混悬液对E.coli、P.aeruginosa、S.aureus 3种细菌具有更好的抗菌效果。结论成功制备了一种硫酸阿米卡星多囊脂质体,其粒径分布均匀、包封率高,释药规律符合Higuchi动力学模型,具有增强的抗菌活性。Objective To prepare amikacin sulfate multivesicular liposomes(AMK-MVLs),to evaluate their quality,and to investigate their antibacterial activity in vitro.Methods The AMK-MVLs suspensionⅠwere prepared by the double-emulsion method.The response surface method of Box-Behnken Design was used to optimize the initial prescription.The AMK-MVLs suspension were obtained by adjusting the drug concentration after washing with saline.The morphology was characterized by optical microscopy and the particle size with its distribution was characterized by the laser granulometer.Differential scanning calorimeter(DSC)was used for phase analysis.The in vitro release behavior was determined by dialysis.Their antibacterial activity in vitro was examined using the microdilution method.Results The optimal formulation process for AMK-MVLs suspension I was as followed:The mass ratio of phospholipid to cholesterol was 1.91:1,the dosage of triolein was 1.02%,and the dosage of PVA was 0.62%.AMK-MVLs were non-concentric spheroids stacked with numerous vesicles.The encapsulation efficiency of AMK-MVLs suspension was 87.12%±1.55%.The average particle size of AMK-MVLs was 11.93μm.DSC results indicated that the drug was dispersed in liposomes in an amorphous state.The in vitro drug release of AMK-MVLs suspension in 72 h was 80%.The hemolytic test showed that there was no risk of hemolysis when the concentration of AMK-MVLs particles was lower than 400μg/mL.The in vitro antibacterial activities of AMK-MVLs suspension on E.coli,P.aeruginosa,and S.aureus were significantly stronger than those of the free AMK.Conclusion An amikacin sulfate multivesicular liposomes was successfully prepared with uniform particle size,good dispersibility,high encapsulation efficiency,sustained drug release behavior,and enhanced antibacterial activity.

关 键 词：硫酸阿米卡星 多囊脂质体 复乳法 Box-Behnken 

分 类 号：R978.1[医药卫生—药品]