雷帕霉素纳米粒滴眼液兔眼部药物分布研究

Research on the pharmaceutical distribution of rapamycin nanometer vector eye drop in rabbit eyes

目的:比较雷帕霉素纳米粒滴眼液及其一般滴眼液滴眼后,在兔眼房水及角膜组织中药物分布。方法:将健康无眼疾新西兰白兔随机分为试验组与对照组,分别每眼结膜囊内单次给雷帕霉素纳米粒滴眼液及其一般滴眼液50μL。于滴眼后15、30、60、360和720min取材,采用高效液相色谱法(HPLC)测定兔眼不同时间房水及角膜组织中雷帕霉素浓度。结果:在用药后15～720min内实验组各时间点房水和角膜组织中的药物浓度均明显高于对照组。实验组内30～720min各时间点房水和角膜组织中的药物浓度比较无统计学差异。结论:雷帕霉素纳米粒滴眼液同一般滴眼液相比明显延长药物在眼部的停留时间,增加房水和角膜组织中的药物浓度,且能够维持组织中药物浓度的平稳。

Objective： To compare the pharmaceutical distribution of rapamycin（RAPA） nanometer vector eye drop with common rapamycin eye drop in rabbit aqueous humor and cornea. Methods： 40 healthy albino rabbits were randomly divided into 2 groups. Each group included 20 rabbits and 4 rabbits （8 eyes） were used at each time points. Each eye received 50μL of rapamycin nanometer vector eye drop in the experimental group, and the same amount of common rapamyein eye drop was given to the control group. The aqueous humors were collected at 15rain, 30rain, 60min, 360min and 720min following topical application of medicine respectively, and the corneas were immediately dissected after being euthanized. The samples from 8 eyes （4 rabbits） were ob- tained at each designed time point. All samples were stored -60°and then were assayed by reversed phase high performance liquid chromatography （HPLC）. Results. The drug levels in aqueous and corneas were significant- ly higher for rapamycin nanometer vector eye drop than common rapamycin eye drop at 15min, 30min, 60min, 360rain and 720min （P 〈 0.05）. The RAPA nano＇particle eye drop can supply a stable RAPA concentration in both aqueous humour and corneas （P 〉 0.05）. Conclusion： The RAPA nano--particle eye drop significant- ly increases the drug penetration and prolongs the residence time in cornea and aqueous humors. The results suggest that RAPA nano--particle eye drop can enhance the ocular bioavailability of RAPA in rabbit eyes.