南方医科大学学报

南方医科大学学报 ›› 2016, Vol. 36 ›› Issue (09): 1237-.

• • 上一篇    下一篇

鬼臼毒素纳米脂质载体的靶向分布

张静，韩凯，王春慧，陈平姣，高琰，王琦，王梦蕾，魏姗姗，杨正慧，胡治丽，曾美，曾抗   

  • 出版日期:2016-09-20 发布日期:2016-09-20

Distribution of podophyllotoxin-loaded nanostructured lipid carriers after topical application on cervical mucosa in Tibet minipigs

  • Online:2016-09-20 Published:2016-09-20

HTML

PDF

790

摘要： 目的观察西藏小型猪宫颈外用鬼臼毒素（POD）纳米脂质载体（POD-NLC）后POD黏膜分布情况和系统毒性作用。方 法应用随机数字表将西藏小型猪分为实验组和对照组，实验组宫颈涂0.5% POD-NLC，对照组涂0.5% POD酊剂。观察24 h 不同时间宫颈黏膜刺激性、POD荧光强度及血中鬼臼毒素含量。结果实验组用药后未发现局部刺激，对照组出现红肿，水 疱、血疱、糜烂、破溃等严重局部刺激反应；药物分布显示对照组在涂药4 h 后黏膜组织中荧光值达到最高；实验组POD荧光 值上升较慢，在16 h 达最大值。实验组用药6 h 后POD的血药浓度达峰值（14.28±0.33 ng/mL），对照组用药4 h 后即达峰值 （42.46±0.32 ng/mL），在所有测试时间点，实验组的血药浓度均低于对照组（P<0.05）。对照组的浓度曲线下面积是实验组的 1.38倍。结论POD-NLC具有缓释性、在黏膜较长时间蓄积，动物实验显示无局部刺激性且系统吸收低。

Abstract: Objective To assess the distribution and systemic toxicity of podophyllotoxin-loaded nanostructured lipid carriers (POD-NLC) after topical application on the cervical mucosa in Tibet minipigs. Methods Twelve Tibet mini-pigs were randomized into test group and control group to receive topical application of 0.5% POD-NLC and 0.5% POD tincture, respectively, on the cervical mucosa. Cervical mucosal irritation, targeted distribution and systemic absorption of POD were observed at different time points within 24 h after the drug application. Results No local inflammation reaction was observed in the test group, while serious local irritations (swelling, blisters, blood blisters, erosion and ulceration) occurred in the control group. The fluorescence intensity of POD in the mucosal tissue reached the peak level at 4 h after drug application in the control group, while the POD fluorescence intensity increased slowly and reached the peak level at 16 h in the test group. The peak blood POD concentration occurred at 6 h after POD-NLC application in the test group (14.28±0.33 ng/mL), as compared to 4 h in the control group (42.46 ± 0.32 ng/mL). At all the time points within 24 h, blood POD concentration remained significantly lower in the test group than in the control group (P<0.05), and the area under curve of blood POD concentration in the control group was 1.38-fold greater than that in the test group. Conclusion POD-NLC allows sustained release of POD and achieves a higher POD concentration in the mucosal tissue without causing local irritation or obvious systemic toxicity in Tibet minipigs.