【摘要】 目的 构建纳米靶向真菌给药系统以提高脂质体在隐球菌感染的肺炎中的药效。方法 采用注射法将钙荧光白-胆固醇琥珀酸单酯(CFW-CHSc)制备成载有两性霉素B的靶向脂质体(CFW-CHSc-Amphotericin B-liposome)。考察CFW-CHSc-AmB-liposome的粒径、ζ电位等。用最小抑菌浓度(MIC)表征CFW-CHSc-AmB-liposome的体外抗真菌活性。使用共聚焦显微镜表征隐球菌摄取载有香豆素6纳米粒(CFW-CHSc-C6-liposome)的效率。用经鼻饲感染的小鼠隐球菌肺炎模型评价CFW-CHSc-AmB-liposome的药效。结果 CFW-CHSc-AmB-liposome呈均匀球型，大小均一，具有良好分散性，并对两性霉素B实现了较高的包载。经CFW-CHSc修饰的脂质体可以提高纳米粒在隐球菌细胞中的递送效率。CFW-CHSc-AmB-liposome在体内外抗隐球菌药效评价中均优于AmB-liposome。结论 经靶向材料CFW-CHSc修饰的脂质体较普通传统脂质体有更高的药物递送效率及药效。更多还原

【Abstract】 Objective To construct a nano targeted fungal drug delivery system to improve the efficacy of liposomes in treatment pneumonia caused by Cryptococcus neofonmans.Methods Amphotericin B targeted liposome(CFW-CHSC-Amphotericin B-liposome) was prepared from calcium fluorescent white-cholesterol succinate monoester(CFW-CHSc) by injection. The particle size and ζ potential of CFW-CHSc-AmB-liposome were investigated. Minimum inhibitory concentration(MIC) was used to characterize the antifungal activity of CFW-CHSc-AmB-liposome in vitro. Confocal microscopy was used to characterize the uptake efficiency of coumarin-6 nanoparticles(CFW-CHSc-C6-liposome) by C. neofonmans. The mice model of Cryptococcus neofonmans pneumonia infected by nasal feeding was used to evaluate the efficacy of CFW-CHSc-AmB-liposome.Results CFW-CHSc-AmB-liposome has a uniform spherical shape, uniform size, good dispersion, and high inclusion of amphotericin B. CFW-CHSc-modified liposomes can improve the delivery efficiency of nanoparticles in C. neofonmans cells. The efficacy of CFW-CHSc-AmB-liposome was superior to that of AmB-liposome in vitro and in vivo against C. neofonmans.Conclusion Targeted liposomes with CFW-CHSc have higher deliveryefficiency and efficacy than conventional liposomes.更多还原