水溶性石墨烯基伊曲康唑滴眼液的制备及其抗真菌活性  

Preparation and antifungal activity of water-soluble graphene-based itraconazole antifungal eye drops

作　　者：李景果 韩奉奇 赵孟阳 何继军 梁珍 张俊杰[1] Li Jingguo;Han Fengqi;Zhao Mengyang;He Jijun;Liang Zhen;Zhang Junjie(Department of Ophthalmology,Henan Province People's Hospital,Henan Eye Hospital,Zhengzhou 450003,China)

机构地区：[1]河南省人民医院眼科,河南省立眼科医院,郑州450003

出　　处：《中华实验眼科杂志》2023年第7期641-645,共5页Chinese Journal Of Experimental Ophthalmology

基　　金：国家自然科学基金项目(52173143)。

摘　　要：目的制备水溶性石墨烯基伊曲康唑滴眼液并评估其抗腐皮镰刀菌活性。方法通过对石墨烯进行氧化改性和高分子材料的修饰策略,制备出水溶性的聚乙二醇修饰石墨烯(GO-PEG)复合材料。通过扫描电子显微镜、表面电位和拉曼光谱等手段对复合材料进行表征。采用溶剂挥发法实现水溶性GO-PEG载体材料对伊曲康唑的负载,获得伊曲康唑滴眼液。采用紫外-可见分光光度计测量伊曲康唑滴眼液的药物负载量;采用微量稀释法和光学显微镜评估伊曲康唑滴眼液的体外抗腐皮镰刀菌效果。结果扫描电子显微镜显示GO-PEG呈二维纳米薄片结构,拥有较多褶皱;表面电位分析显示GO-PEG的表面电位为-42.40 mV;拉曼光谱显示GO-PEG的ID/IG为1.003。水溶性GO-PEG载体负载最大的伊曲康唑药物质量浓度为10 mg/ml,相比于伊曲康唑的水溶解度(0.001 mg/ml),表观溶解度提高了10 000倍。伊曲康唑滴眼液对腐皮镰刀菌的最低抑菌质量浓度约为1.88 μg/ml,载体材料GO-PEG对腐皮镰刀菌无明显抗菌活性。结论 GO-PEG实现了对伊曲康唑的有效负载和增溶,表现出对体外腐皮镰刀菌的抑制作用。Objective To prepare water-soluble graphene-based itraconazole antifungal eye drops and evaluate its antifungal activity against Fusarium solani.Methods By oxidative modification of graphene and modification of polymer materials,water-soluble graphene oxide-modified polyethylene glycol(GO-PEG)composites were prepared.The composites were characterized by scanning electron microscopy,zeta potential,and Raman spectroscopy.The antifungal drug itraconazole was loaded onto the GO-PEG vector by solvent evaporation method,and itraconazole eye drops were obtained.The drug loading of itraconazole eye drops was measured using a UV and visible spectrophotometer.The antifungal effect in vitro was assessed by the microdilution method and light microscopy.Results Scanning electron microscopy showed that GO-PEG had a two-dimensional nanosheet structure and many wrinkles.The zeta potential of GO-PEG was-42􀆰40 mV.Raman spectroscopy showed that the ID/IG of GO-PEG was 1􀆰003.Using the water-soluble GO-PEG vector,a maximum itraconazole concentration of 10 mg/ml was achieved with a 10000-fold increase in apparent solubility(10 mg/ml vs 0􀆰001 mg/ml).The antifungal results showed that the minimum inhibitory concentration of itraconazole eye drops against Fusarium solani was approximately 1􀆰88μg/ml,but the GO-PEG vector has no significant antifungal activity against Fusarium solani.Conclusions GO-PEG achieves effective loading and solubilization of itraconazole,demonstrating an in vitro inhibitory effect on Fusarium solani.

关 键 词：抗真菌药物 伊曲康唑 溶解性 真菌性角膜炎 抗真菌性能 

分 类 号：TQ460.4[化学工程—制药化工]