伏立康唑TPGS-Cremophor EL眼用纳米胶束的制备及体外抗白色念珠菌评价  

Preparation of voriconazole-loaded TPGS-Cremophor EL ophthalmic nanomicelles and evaluation of its anti-Candida albican efficacy in vitro

作　　者：曾甜 王欣宜 彭澳 刘雪 文宝程 王凯月 田宝成[1] ZENG Tian;WANG Xinyi;PENG Ao;LIU Xue;WEN Baocheng;WANG Kaiyue;TIAN Baocheng(Department of Pharmaceutics,School of Pharmacy,Binzhou Medical University,Yantai 264003,Shandong,P.R.China)

机构地区：[1]滨州医学院药学院药剂学教研室,山东烟台264003

出　　处：《滨州医学院学报》2024年第1期26-31,共6页Journal of Binzhou Medical University

基　　金：国家自然科学基金(81703717)。

摘　　要：目的构建基于α-生育酚聚乙二醇琥珀酸酯-聚氧乙烯蓖麻油EL的眼用混合胶束,并负载抗菌药物伏立康唑(TPGS-EL/VRC),探讨该纳米胶束的眼部药物递送性能及体外抗白色念珠菌效果。方法薄膜水化法制备TPGS-EL/VRC混合胶束,纳米激光粒度仪测定其粒径分布与Zeta电位,透射电子显微镜考察其形貌,高效液相色谱法测定载药量及包封率。通过细胞毒性试验和鸡胚绒毛尿囊膜(HET-CAM)试验评价TPGS-EL/VRC的体外生物相容性。利用流式细胞仪研究角膜上皮细胞(HCE-T)对纳米胶束的摄取能力及细胞摄取途径。通过体外抗真菌活性试验和抑菌环试验评估纳米胶束对白色念珠菌C.albican的抗菌能力。结果TPGS-EL/VRC混合胶束粒径为(109.63±0.25)nm,电位为(-29.3±0.20)mV,呈球形粒子,对VRC具有较好的包封率。纳米胶束对HCE-T细胞毒性低,生物相容性好。TPGS-EL混合胶束有效提高了HCE-T细胞对药物的摄取,为溶液组的5.8倍。在两种体外培养模型中均表现出更好的抗白色念珠菌能力。结论TPGS-EL/VRC纳米胶束具有良好的制剂学性质及生物相容性,展示了优异的促进VRC细胞内转运性能及体外抗白色念珠菌药效,为临床眼部真菌疾病的高效治疗提供了一种创新递送载体。Objective To construct ophthalmic nanomicelles based onα-tocopheryl polyethylene glycol succinate-polyoxyethylene castor oil for loading the antibacterial drug voriconazole(TPGS-EL/VRC),and to investigate its ocular drug delivery performance and in vitro anti-Candida albican efficacy.Methods TPGS-EL/VRC mixed micelles were prepared by thin film hydration method.The particle size distribution and Zeta potential of the micelles were measured by a particle size analyzer.The morphology of the micelles was investigated by transmission electron microscope.High performance liquid chromatography(HPLC)was used to determine the drug loading and encapsulation efficiency.The in vitro biocompatibility of TPGS-EL/VRC was evaluated by cytotoxicity assay and hen's egg test-chorioallantoic membrane(HET-CAM).The uptake capacity of corneal epithelial cells(HCE-T)to nanomicelles and its uptake pathway were studied by flow cytometry.The antibacterial activity of nanomicelles against Candida albicans was evaluated by in vitro antifungal activity assay and ring inhibition assay.Results TPGS-EL/VRC mixed micelles were spherical particles with a particle size of(109.63±0.25)nm and potential of(-29.3±0.20)mV,and showed good encapsulation efficiency for VRC.TPGS-EL/VRC had low cytotoxicity to HCE-T cells and were biocompatible.TPGS-EL nanomicelles effectively increased the uptake of drugs by HCE-T cells by 5.8 times that of the normal solution group,and showed better anti-candida albicans efficacy in both in vitro models.Conclusion TPGS-EL/VRC nanomicelles demonstrated excellent formulation properties,biocompatibility,and improved intracellular transport of VRC and in vitro anti-Candida albicans efficacy.As a result,it provides an innovative delivery vehicle for the efficient treatment of ocular fungal infections.

关 键 词：伏立康唑 α-生育酚聚乙二醇琥珀酸酯 纳米胶束 

分 类 号：R944[医药卫生—药剂学]