生物黏附性环孢素纳米脂质载体的制备及其兔泪液消除动力学  

Preparation of bioadhesive cyclosporine-nanostructured lipid carrier and its eliminating kinetics in rabbit tears

作　　者：鲍晓[1] 肖衍宇[1] 牛江秀[1] 平其能[1] 

机构地区：[1]中国药科大学药剂学教研室,江苏南京210009

出　　处：《中国新药与临床杂志》2011年第7期511-516,共6页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家重大新药创制科技重大专项(2009ZX09310-004);中央高校基本科研业务费专项资金资助(JKQ2009018)

摘　　要：目的制备具有生物黏附性的环孢素纳米脂质载体(NLC)眼用制剂并考察其在家兔泪液中的消除情况。方法采用熔融-乳化法制备NLC,用生物黏附性材料普流罗尼F127(F127)调节制剂黏度,用Zetasizer纳米粒度仪测定纳米粒粒径,HPLC法考察制剂在家兔泪液中不同时间点药物浓度,以未加入F127的NLC作对照,采用Kinetica4.4计算药动学参数。结果 NLC粒径(35.9±0.2)nm,F127-NLC粒径(41.2±0.2)nm。NLC中F127的含量影响制剂的稳定性,高浓度的F127(9.0%)降低NLC的稳定性,而低浓度的F127(≤6.0%)增加NLC的稳定性。含F127 1.7%、3.3%和6.0%的F127-NLC在兔眼部经6h的泪液消除动力学参数AUC分别为NLC的1.57、1.79和2.42倍,MRT分别为NLC的1.19、1.31和1.90倍。结论加入6.0%的F127制备的NLC可显著提高药物在泪液中的浓度,延长作用时间,减少刺激性。AIM To prepare the bioadhesive cyclosporine （CsA）-nanostructured lipid carriers （NLC） and study the eliminating behavior in rabbit tears. METHODS The melt-emulsification method was chosen to prepare NLC. Lutrol F127 （F127） was used to increase the viscosity of the eye drops. The particle size was determined by Zetasizer. HPLC method was used to determine the drug concentration in the rabbit tears at different times, and pharmacokinetics parameters were calculated by Kinetica4.4. RESULTS The mean particle sizes of NLC and F127 coated NLC （F127-NLC） were （35.9 ±0.2） nm and （41.2 ± 0.2） nm, respectively. The concentration of F127 could influence the stability of NLC： the stability would be decreased with high concentration of F127 （9.0%） while increased with low concentration （≤ 6.0%）. The area under CsA concentration-time curve （AUC） of F127-NLC added with 1.7%, 3.3% and 6.0% of F127 in the rabbit tears during 6 hours was 1.57, 1.79 and 2.42-fold of NLC, while the mean residence time （MRT） was 1.19, 1.31 and 1.90-fold of NLC, respectively. CONCLUSION The prepared CsA-NLC added with 6.0% of F127 can markedly improve the concentration of CsA in the rabbit tears, and prolong the acting time and lower irritation for eyes.

关 键 词：环孢菌素 生物黏附性 纳米结构 药物载体 普流罗尼F127 眼泪 消除动力学 

分 类 号：R961[医药卫生—药理学]