醋酸卡泊芬净单硬脂酸甘油酯纳米粒抗白色念珠菌感染的增效作用研究  

Study on the synergistic antifungal effects of caspofungin acetate loaded glyceryl monostearate nanoparticle on Candida albicans

作　　者：郭灵怡 刘艳超 高路[3] 刘瑞瑶 吕权真 俞媛 GUO Lingyi;LIU Yanchao;GAO Lu;LIU Ruiyao;LYU Quanzhen;YU Yuan(Department of Pharmacy,Naval Medical University,Shanghai 200433,China;Department of Clinical Pharmacy,Shanghai General Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200080,China;Department of Pharmacy,Shanghai Tenth People’s Hospital,School of Medicine,Tongji University,Shanghai 200092,China)

机构地区：[1]海军军医大学药学系,上海200433 [2]上海交通大学附属第一人民医院临床药学科,上海200080 [3]同济大学附属第十人民医院药学部,上海200072

出　　处：《药学实践与服务》2025年第3期136-142,150,共8页Journal of Pharmaceutical Practice and Service

基　　金：国家自然科学基金(82273487);全军医学科技青年培育计划(21QNPY051);上海市青年科技英才扬帆计划(21YF1436300)。

摘　　要：目的制备醋酸卡泊芬净单硬脂酸甘油酯固体脂质纳米粒(CAS-SLNs)并进行表征,考察纳米粒的体内外抗白色念珠菌活性。方法建立醋酸卡泊芬净(CAS)高效液相色谱检测的方法。熔融法制备CAS-SLNs并进行表征,测定其最低抑菌浓度(MIC)以及对白色念珠菌生物被膜的抑制效果。建立小鼠白色念珠菌系统性感染模型,给药后考察动物的体重和肾脏载菌量变化,评价纳米粒的药效学。结果CAS在HPLC保留时间为6.8 min,线性关系良好,精密度、稳定性符合测定要求。透射电镜观察CAS-SLNs呈类圆球状,粒径(135.97±1.73)nm,Zeta电位(19.33±0.37)m V,载药量(7.55±0.68)%,包封率(67.71±1.74)%。体外实验表明,CAS-SLNs具有显著的抑菌效果,MIC为9.78×10-4μg/ml,优于CAS以及CAS与GMS的物理混合组,并具有显著的生物被膜抑制作用(P<0.001)。体内研究表明,在白色念珠菌侵袭性感染模型中,CAS-SLNs较对照组(P<0.01)、CAS组体重恢复更加显著,并且CAS-SLNs相对CAS组显著降低了小鼠肾脏载菌量(P<0.05)。结论CAS-SLNs可以显著增强CAS的体内外抗白色念珠菌效果,为CAS的剂型改造提供了有益参考。Objective To prepare and characterize caspofungin acetate-loaded solid lipid nanoparticles using glycerol monostearate(CAS-SLNs),and investigate the antifungal effect of potentiation on Candida albicans in vitro and in vivo.Methods A high performance liquid chromatography method was established for the determination of caspofungin acetate(CAS).CAS-SLNs were prepared by the melt-emulsification method and characterized.The minimum inhibitory concentration(MIC)and the inhibitory effect on Candida albicans biofilm were determined.A systemic infection model of Candida albicans was established in mice,and the growth curve models for body weight and fungal load of kidneys of the animals were investigated after intravenous infection.Results The retention time of CAS was 6.8 min.The calibration curve showed good linearity,and the precision and stability met the requirements of the assay.Transmission electron microscopy revealed that CAS-SLNs were spherical,with a particle size of(135.97±1.73)nm.The Zeta potential was(19.33±0.37)mV,drug loading was(7.55±0.68)%,and encapsulation efficiency was(67.71±1.74)%.CAS-SLNs showed significant in vitro antifungal inhibition with a MIC of 9.78×10-4 g/ml,which was significantly better than CAS group and the physical mixture group of CAS and GMS,as well as the same biofilm inhibition was observed(P<0.001).Pharmacodynamic studies demonstrated that CAS-SLNs maintained stable body weight gain compared to the control(P<0.01)and CAS groups in Candida albicans invasive infection model,and that CAS-SLNs significantly reduced renal fungal burden load relative to the CAS group(P<0.05).In vivo study revealed that a stable body weight was maintained in CAS-SLNs group compared to the control group(P<0.01)in Candida albicans invasive infection model.CAS-SLNs also significantly reduced renal fungal load compared to the CAS group(P<0.05).Conclusion CAS-SLNs significantly enhanced the antifungal effects of CAS in vitro and in vivo,which provided a valuable insight for the research of new formulati

关 键 词：白色念珠菌 醋酸卡泊芬净 单硬脂酸甘油酯纳米粒 协同抗菌 

分 类 号：R943[医药卫生—药剂学] R965[医药卫生—药学]