伊曲康唑甘草酸纳米胶束的构建及抗白念珠菌作用研究  

Glycyrrhizic acid nanomicelles loaded with itraconazole and its antiCandida albicans effect

作　　者：彭澳 刘雪[1] 刘洋 曾甜 闫文浩 于慧 田宝成 PENG Ao;LIU Xue;LIU Yang;ZENG Tian;YAN Wen-hao;YU Hui;TIAN Bao-cheng(BinzhouMedical University,Yantai Shandong 264003)

机构地区：[1]滨州医学院,山东烟台264003

出　　处：《中南药学》2025年第2期430-435,共6页Central South Pharmacy

摘　　要：目的构建负载伊曲康唑的甘草酸纳米胶束(ICZ-NMs),并对其进行表征及眼部应用的细胞学与体外抗白念珠菌作用评价。方法采用注入法制备ICZ-NMs,测定其粒径、Zeta电位、包封率、载药量、药物的物相状态和初步稳定性,并观察其微观形貌。采用CCK-8法考察其对人永生化角膜上皮细胞(HCE-T)的毒性。采用流式细胞术考察纳米胶束的入胞能力和摄取途径。采用体外抑菌率和纸片琼脂板抑菌圈评价ICZ-NMs对白念珠菌株Candida albicans SC5314的体外抗菌作用。结果所制ICZ-NMs的纳米胶束粒径为(152.4±4.2)nm,Zeta电位为(-25.1±0.9)mV,包封率为66.2%,载药量为11.0%。透射电子显微镜显示微观形态圆整。在4℃下存放7 d的稳定性良好。差示扫描量热图谱确证ICZ-NMs中ICZ以无定形形态存在。细胞毒性考察结果显示,500μg·mL^(-1)的空白胶束(NMs)和载药浓度为100μg·mL^(-1)的ICZ-NMs胶束对HCE-T细胞无毒。纳米胶束可提高药物的入胞效率,其主要的细胞摄取机制为巨胞饮作用。在体外抑菌率和纸片琼脂板抑菌圈评价中,ICZ-NMs均显示出比游离ICZ更强的抗菌作用。结论成功构建了ICZ-NMs纳米胶束,增加了HCE-T细胞内的药物递送,提高了ICZ的体外抗白念珠菌作用,且所制的ICZ-NMs眼部应用时生物相容性好。Objective To construct glycyrrhizic acid nanomicelles loaded with itraconazole(ICZ-NMs),characterize their pharmaceutical properties and evaluate its cytology and in vitro anti-Candida albicans effects for ophthalmic use.Methods ICZ-NMs were prepared with the injection method,and its particle size,Zeta potential,encapsulation efficiency,drug loading,phase state and preliminary stability were determined.The micromorphology was also observed.The cytotoxicity to human immortalized corneal epithelial cells(HCE-T)was determined by CCK-8 assay.The endocytosis and uptake pathway of nanomicelles were investigated by flow cytometry.The in vitro antibacterial effect of ICZ-NMs against Candida albicans SC5314 was evaluated by antibacterial rate and agar diffusion from paper discs.Results The prepared ICZ-NMs had a particle size of(152.4±4.2)nm,Zeta potential of(-25.1±0.9)mV,an encapsulation efficiency of 66.2%and a drug loading of 11.0%.Transmission electron microscopy showed spherical and intact morphology.The stability was good after 7 d of storage at 4℃.Differential scanning calorimetry confirmed the presence of ICZ in ICZ-NMs amorphously.The cell experiments showed that neither blank micelles(NMs,500μg·mL^(-1))nor ICZ-NMs loaded with ICZ(100μg·mL^(-1))showed toxicity to HCE-T cells.Nanomicelles improved the efficiency of drug entry into the cell,and the major entry mechanism was macropinocytosis.In evaluation of both the in vitro antibacterial rate and the agar diffusion from paper discs assays,ICZ-NMs showed stronger antibacterial effect than that of free ICZ.Conclusion ICZ-NMs nanomicelles are successfully constructed,which increases drug delivery into HCE-T cells,improves the in vitro anti-Candida albicans effect of ICZ,and demonstrates good biocompatibility for ophthalmic use.

关 键 词：伊曲康唑 甘草酸 纳米胶束 白念珠菌 

分 类 号：R944[医药卫生—药剂学] R96[医药卫生—药学]