布替萘芬纳米胶束兔眼局部点眼药代动力学研究  

Ocular pharmacokinetics of topical administration of butenafine nanomicelles in rabbit eyes

作　　者：卢萍 梁珍 张振 杨晶晶 宋菲 李景果 周天洋 张俊杰 Lu Ping;Liang Zhen;Zhang Zhen;Yang Jingjing;Song Fei;Li Jingguo;Zhou Tianyang;Zhang Junjie(Henan Eye Institute,Henan Eye Hospital,Henan Provincial People's Hospital,Zhengzhou University People's Hospital,Henan University People's Hospital,Zhengzhou 450003,China)

机构地区：[1]河南省立眼科医院,河南省眼科研究所,河南省人民医院,郑州大学人民医院,河南大学人民医院,郑州450003

出　　处：《中华实验眼科杂志》2020年第12期1038-1044,共7页Chinese Journal Of Experimental Ophthalmology

基　　金：国家自然科学基金联合重点项目(U1704283);河南省科技厅基础与前沿项目(142300410057)。

摘　　要：目的研究广谱抗真菌药物布替萘芬纳米胶束(BTF-NM)兔眼局部点眼后的药代动力学。方法采用自组装法制备BTF-NM,利用纳米粒度-Zeta电位分析仪测定BTF-NM的粒径、多分散系数(PDI)和Zeta电位;采用高效液相色谱法(HPLC)测定包封率。取健康无眼疾新西兰白兔42只,采用随机数字表法将实验兔分为BTF-NM组和布替萘芬混悬剂(BTF-S)组,2个组均采用相应药物双眼结膜囊内点眼,单次点眼50μl。分别于点眼后5、15、30、60、120、180和240 min将直径7.5 mm滤纸片置于兔眼结膜囊内,停留1 min后取出,以收集泪液样品,然后经兔耳缘静脉注射质量分数4%戊巴比妥钠溶液处死实验兔,抽取房水,剖取角膜组织,利用HPLC检测各样本组中布替萘芬(BTF)药物浓度。结果BTF-NM的粒径为(15.65±0.04)nm,PDI为0.11±0.01,Zeta电位为(-0.29±0.36)mV,包封率为(98.38±0.29)%。BTF-NM组单次点眼后泪液和角膜组织中药物达峰时间(T max)均为5 min,药物峰质量分数分别为(485.21±66.29)μg/g和(12.53±2.32)μg/g,分别是BTF-S组的5.6倍和78倍,在观察时间内,BTF-NM组泪液和角膜中各时间点的药物质量分数显著高于对应时间点BTF-S组的药物质量分数,差异均有统计学意义(均P<0.01)。BTF-NM组泪液和角膜的药物浓度-时间曲线下面积(AUC)0-240 min分别为7488.90(μg/g)·min和829.01(μg/g)·min,分别是BTF-S组的7.2倍和52倍。BTF-NM组和BTF-S组的房水中均未检测到药物。结论BTF-NM的制备工艺简单,包封率高,粒径小。与BTF-S相比,BTF-NM制剂可明显提高BTF在兔眼角膜中的生物利用度。Objective To study the pharmacokinetics of the broad-spectrum antifungal drug butenafine nanomicelles(BTF-NM)after topical instillation.Methods The self-assembly method was used to prepare BTF-NM.The particle size,Zeta potential,and polydispersity index(PDI)of BTF-NM were measured by a nano-particle size-Zeta potential analyzer,and the encapsulation efficiency was determined by high-performance liquid chromatography(HPLC).Forty-two healthy New Zealand white rabbits without eye disease were randomly divided into the BTF-NM group and the BTF suspension(BTF-S)group.The corresponding drugs were instilled in the conjunctival sac with a single instillation of 50μl.The 7.5 mm filter paper was placed in the conjunctival sac of rabbit eye for 1 minute at 5,15,30,60,120,180,240 minutes after the administration.Then the rabbits were sacrificed by intravenous injection of 4%sodium pentobarbital solution through the ears of the rabbits.The aqueous humor was extracted and the corneal tissue was dissected.The drug concentration of BTF in different tissues was measured by HPLC.The study was approved by the Life Science Ethics Review Committee of Henan Eye Hospital(No.HNEECA-2019-01).Results The particle size and PDI of BTF-NM were(15.65±0.04)nm and 0.11±0.01,respectively,the Zeta potential was(-0.29±0.36)mV,the encapsulation rate was(98.38±0.29)%.The peak time of the drug both in tears and corneal tissues after BTF-NM application was 5 minutes.The peak concentrations of the drug in tears and corneas of the BTF-NM group were(485.21±66.29)μg/g and(12.53±2.32)μg/g,which were 5.6 and 78 times than that of the BTF-S group,respectively.Within the observation time,the mass fractions of the drug in tears and corneas of the BTF-NM group at each time point were significantly higher than those of BTF-S group at corresponding time points(all at P<0.01),respectively.The area under the concentration-time curve(AUC)0-240 minutes in tears and corneas of the BTF-NM group was 7488.90(μg/g)·minute and 829.01(μg/g)·minute,which was 7.2

关 键 词：布替萘芬 纳米胶束 眼药代动力学 兔 高效液相色谱法 

分 类 号：R965[医药卫生—药理学]