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
投稿时间:2023-10-22  修订日期:2024-05-30  点此下载全文
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作者单位邮编
郭灵怡 中国人民解放军海军军医大学药学系 210000
俞媛 中国人民解放军海军军医大学药学系 210000
基金项目:国家自然科学基金项目(面上项目,重点项目,重大项目)
中文摘要:[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)以及对白念珠菌生物被膜的抑制效果。建立小鼠白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 mV,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9.78×10-4 mg/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,P<0.001)。体内研究表明,在白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的体内外抗白念珠菌效果,为CAS的剂型改造提供了有益的参考。
中文关键词:白念珠菌  醋酸卡泊芬净  单硬脂酸甘油酯纳米粒  协同抗菌
 
Study on the synergistic antifungal effects of Caspofungin Acetate loaded glyceryl monostearate nanoparticle against Candida albicans
Abstract:[Abstract] Objective To prepare and characterize caspofungin acetate-loaded solid lipid nanoparticles using glycerol monostearate (CAS-SLNs), and investigate the antifungal effect of potentiation against 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, 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, providing a valuable insight for the research of new formulation of CAS.
keywords:Candida albicans  Caspofungin Acetate  glyceryl monostearate solid lipid nanoparticles  synergistic antifungal
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