摘要
目的:将阳离子型药物盐酸倍他洛尔(BH),与具有离子交换性能的蒙脱石及聚丙烯酸树脂联合使用制备新型盐酸倍他洛尔/蒙脱石聚丙烯酸树脂微球(Mt-BH-MP)新型眼用微纳米混悬剂,考察其刺激性及眼前端滞留能力。方法:采用油包油乳化-溶剂挥发法制备微球,以BH水溶液和市售贝特舒为对照,分别采用永生化人角膜上皮细胞(iHCECs)构筑角膜前滞留的细胞模型和荧光示踪法评价Mt-BH-MP在细胞模型及兔眼眼表的滞留能力;以MTT法、兔眼眨眼实验及角膜荧光损失来共同评价该新型给药系统的刺激性。结果:iHCECs细胞模型角膜前滞留实验结果表明,Mt-BH-MP的眼部滞留能力明显优于贝特舒组和BH水溶液组;Mt-BH-MP兔眼在体角膜前荧光可维持(46±1)min,亦明显长于BH水溶液和贝特舒滴眼液组(P<0.05),上述二项实验结果一致。MTT实验结果显示,iHCECs与各制剂接触2 h后,细胞存活率大小顺序为:空白微球>Mt-BH-MP>BH水溶液>贝特舒;兔眼眨眼刺激性及荧光角膜损伤实验结果表明,Mt-BH-MP给药后并无明显异物感及角膜机械损伤。结论:制备的新型微球眼部递药系统具有良好的眼部滞留能力且刺激性相对较小,具有良好的眼部递药应用前景。
OBJECTIVE To prepare a new ophthalmic micro-and nano-suspension of betaxolol hydrochloride/montmorillonite polyacrylic acid resin microspheres(Mt-BH-MP)by combining the cationic drug betaxolol hydrochloride(BH)with montmorillonite and polyacrylic acid resin with ion exchange properties,and to investigate its irritation and anterior eye retention.METHODS Microspheres were prepared by Oil1/Oil2 emulsification-solvent evaporation method.The BH aqueous solution and the commercially available Betoptic eye drops were used as the control group.Retention capacity of Mt-BH-MP was evaluated by fluorescent tracer method and pre-corneal retention cell model was constructed by immortalized human corneal epithelial cells(iHCECs).The irritation of the novel drug delivery system was jointly evaluated by the MTT method,the rabbit eye blink test,and the corneal fluorescence damage.RESULTS The results of pre-corneal retention test showed that the retention ability of Mt-BH-MP was significantly better than that of Betoptic and BH aqueous solution.In the fluorescent tracer experiment of rabbit eyes,the fluorescence of Mt-BH-MP rabbits could maintain(46±1)min,which was significantly longer than BH aqueous solution and Betoptic eye drops(P<0.05)and was consistent with above iHCECs pre-corneal retention test result.The results of MTT assay showed that after iHCECs were exposed to each formulation for 2 hours,the order of cell survival rate was as follows:blank microspheres>Mt-BH-MP>BH aqueous solution>Betasol;the results of blink irritation and fluorescence corneal injury test in rabbit eyes showed that Mt-BH-MP had no significant foreign body sensation or corneal mechanical injury after administration.CONCLUSION The new microsphere ocular drug delivery system has characteristcs of good ocular retention and less irritation,which indicate a good application prospect.
作者
韩鑫玥
刘朔
赵雅文
李娟
刘晗雨
潘育方
杨帆
陈燕忠
吕竹芬
平其能
李薇
侯冬枝
HAN Xin-yue;LIU Shuo;ZHAO Ya-wen;LI Juan;LIU Han-yu;PAN Yu-fang;YANG Fan;CHEN Yan-zhong;LYU Zhu-fen;PING Qi-neng;LI Wei;HOU Dong-zhi(Guangdong Provincial Key Laboratory of Advanced Drug Delivery,Guangdong Engineering and Technology Research Center of Topical Pricise Drug Delivery System,School of Pharmacy,Guangdong Pharmaceutical University,Guangdong Guangzhou 510006,China;Departmentof Pharmaceutics,China Pharmaceutical University,Jiangsu Nanjing 210009,China;Guangzhou Institute for Drug Control,Guangdong Guangzhou 510160,China)
出处
《中国医院药学杂志》
CAS
北大核心
2020年第3期254-259,共6页
Chinese Journal of Hospital Pharmacy
基金
国家自然科学基金项目(编号:51102052)
广东省医学科学技术研究项目(编号:A2016275).
关键词
微球
蒙脱石
角膜前滞留
永生化人角膜上皮细胞
microspheres
montmorillonite
anterior corneal retention
immortalized human corneal epithelial cells
作者简介
韩鑫玥,男,硕士研究生,电话:17818528814,E-mail:591885592@qq.com;通讯作者:侯冬枝,女,博士,副教授,研究方向:药物新剂型与新制剂研究,电话:18026312508,E-mail:houdongzhi406@163.com