司帕沙星阳离子脂质体原位凝胶兔角膜滞留性考察

In vivo rabbit corneal retention of ocular sparfloxacin cationic liposomal in-situ gels

目的制备司帕沙星(SF)阳离子脂质体-原位凝胶(ISG),并对其在兔角膜的滞留性进行考察。方法采用pH梯度法制备SF脂质体(SFL),用N-三甲基壳聚糖(TMC60)包衣制备SF阳离子脂质体(TMC60-SFL),再与泊洛沙姆407为基质的凝胶混合制备TMC60-SFL-ISG。采用荧光示踪法对其兔角膜的滞留时间进行考察,并与SFL、TMC60-SFL及未包衣的SFL-ISG进行比较。同时对包衣及未包衣的SFL-ISG进行眼刺激性考察。结果与SFL比较,TMC60-SFL的兔角膜滞留性无明显变化,而未包衣的SFL-ISG及TMC60-SFL-ISG在兔角膜的滞留时间均有不同程度的延长(P<0.05),且以TMC60-SFL-ISG的延长效果最显著,与未包衣的SFL-ISG比较差异有统计学意义(P<0.05)。与空白ISG比较,包衣及未包衣的SFL-ISG对家兔眼均无明显刺激性。结论 TMC-SFL-ISG结合阳离子脂质体和ISG的特点,能明显延长兔角膜滞留时间,值得进一步研发。

Objective To investigate the rabbit corneal retention of ocular cationic liposomal in-situ gels（ISG） containing sparfloxacin（SF）.Methods SF liposomes（SFL） were prepared by pH gradient method followed by N-trimethyl chitosan（TMC60） coating（TMC60-SFL）.Poloxamer 407 was used as the base of the ISG mixed with TMC60-SFL to obtain TMC60-SFL-ISG.The residence in rabbit eyes was observed with fluorescence tracer method and compared with that of SFL,TMC60-SFL and SFL-ISG without TMC60-coating.The eye irritation of TMC60-SFL-ISG and SFL-ISG was studied as well.Results Compared with that of SFL,the corneal retention time of TMC60-SFL showed no significant change,while that of SFL-ISG without TMC60-coating and TMC60-SFL-ISG was prolonged significantly（P〈0.05）,and the retention time of TMC60-SFL-ISG was the longest with notable differences with that of SFL-ISG without TMC60-coating（P〈0.05）.Compared with the blank ISG,TMC60-SFL-ISG and SFL-ISG showed no significant irritation to the rabbit eyes.Conclusion TMC60-SFL-ISG show the advantages of cationic liposomes and ISG with prolonged corneal retention,which are valuable to be studied further.