温敏型透明质酸/巯基化壳聚糖眼用复合纳米凝胶的制备与评价  

Preparation and evaluation of thermo-sensitive hyaluronic acid /thiolated chitosan ophthalmic complex nano-hydrogel

作　　者：姜美霞[1] 熊慧[1] 李樾[1] 周建平[1] 姚静[1] 

机构地区：[1]天然药物活性组分与药效国家重点实验室(中国药科大学),药剂学教研室,南京210009

出　　处：《中国药科大学学报》2014年第4期413-419,共7页Journal of China Pharmaceutical University

基　　金：江苏省自然科学基金资助项目(No.SBK201322347);天然药物活性组分与药效国家重点实验室资助项目(No.JKGQ201107);中国药科大学中央高校基本科研业务费专项资金资助项目(No.JKPZ2013005);青蓝工程;国家基础科学人才培养基金资助项目(No.J0630858);国家级大学生实践创新训练计划资助项目~~

摘　　要：制备温敏型的透明质酸衍生物(HA-PN)与巯基化壳聚糖(CMCS-NAC)的复合纳米凝胶(HP/CN),并对其药代动力学性质进行评价。采用孵育法制备环孢素A(CsA)复合纳米凝胶(CsA HP/CN),测定其粒度分布、Zeta电位、低临界溶解温度(LCST)和载药量等理化性质。以家兔为模型动物进一步评价了CsA HP/CN制剂眼部刺激性、黏附性和眼部药代动力学。制得的CsA HP/CN为球形,粒径(122.7±17.8)nm,Zeta电位-(27.87±2.16)mV,LCST约为28.4℃,载药量最高可达15.08%。CsA HP/CN制剂对兔眼无刺激性;滴眼后15 min,制剂组的黏附性是单独载体(对照组)的1.97倍;家兔眼部AUC以及MRT显著提高,分别是对照组的1.67和5.17倍。所制备的CsA HP/CN粒径小、载药量高,可明显延长CsA在眼部的滞留时间,提高其生物利用度,是一个非常有应用前景的眼部递药系统。The aim of this research was to prepare and evaluate thermo-sensitive complex nano-hydrogel（ HP/ CN） comprising of hyaluronic acid derivative （HA-PN） and thiolated chitosan （CMCS-NAC） for the ocular delivery of cyclosporine A （CsA）. The CsA complex nano-hydrogel（ CsA HP/CN） was prepared by incubation, then the size, Zeta potential, low critical solution temperature （LCST） and drug-loading capacity were characterized. The rabbit eye irritation effect, tissue adhesiveness and pharmacokinetic studies were investigated to evaluate the ocular compatibility and bioavailability of CsA HP/CN formulation. CsA HP/CN was found to be spherical in shape with a mean diameter of （ 122.7 ±17.8） nm, the Zeta potential of - （27.87 ±2. 16） mV and LCST of 28.4 ℃ with a drug-loading capacity up to 15.08%. The rabbit eye irritation experiment showed no irritation on rabbit eyes. The CsA HP/CN group displayed significantly higher adhesive effect （ 1.97- fold） on eye tissue as compared to the control group （ drug carrier alone） after 15 min of ocular administration. Rabbit eyes pharmacoki- netic data confirmed significantly higher AUC （ 1.67- fold） and MRT （ 5.17- fold） compared to the control group. Therefore, CsA HP/CN with small particle size and high drug loading capacity could obviously extend the drug retention time and increase its bioavailability on eyes, thus with potential application prospect in ocular drug delivery system.

关 键 词：复合纳米凝胶 HA-PN CMCS-NAC 环孢素A 

分 类 号：R943[医药卫生—药剂学]