[1]刘丽诗,韩凯,王琦,等.0.5%鬼臼毒素纳米脂质载体在阴道黏膜的毒性试验[J].南方医科大学学报,2018,(12):1527.[doi:10.12122/j.issn.1673-4254.2018.12.21]
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0.5%鬼臼毒素纳米脂质载体在阴道黏膜的毒性试验()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2018年12期
页码:
1527
栏目:
出版日期:
2018-12-31

文章信息/Info

Title:
Acute and chronic toxicity of 0.5% podophyllotoxin-loaded nanostructured lipid carriers to vaginal mucosa in rabbits and rats
作者:
刘丽诗韩凯王琦高琰王晶莹曾抗
关键词:
鬼臼毒素纳米脂质载体刺激性急性毒性长期毒性尖锐湿疣
Keywords:
podophyllotoxin nanostructured lipid carrier irritation acute toxicity chronic toxicity condyloma acuminate
DOI:
10.12122/j.issn.1673-4254.2018.12.21
摘要:
目的考察0.5%鬼臼毒素纳米脂质载体在阴道黏膜的安全性。方法(1)刺激性试验:将12只新西兰兔均分为3组,分别予 生理盐水(NS)、0.5%鬼臼毒素酊剂(POD-T)和0.5%鬼臼毒素纳米脂质载体(POD-NLC),阴道给药10 d后取阴道组织行病理检 查,根据Eckstein评分标准进行评估。(2)急性毒性试验:将20只SD雌性大鼠均分2 组,分别予赋形剂和POD-NLC,以300倍临 床剂量在24 h内分3次阴道给药,连续观察14 d后解剖并计算脏器系数。(3)长期毒性试验:80只SD雌性大鼠均分4组,分别予 赋形剂、低剂量POD-NLC(15倍临床剂量)、中剂量POD-NLC(30倍临床剂量)和高剂量POD-NLC(60倍临床剂量)。连续13 周每日阴道给药1次,每周记录体质量,给药结束后对每组2/3的大鼠进行抽血化验、解剖并计算脏器系数和肝脏组织病理学检 查。为观察药物延迟毒性,每组剩余1/3的大鼠停药观察2周后做同前处理。结果(1)刺激性试验:0.5% POD-NLC对阴道黏膜 为极轻刺激性,0.5% POD-T为中度刺激性;(2)急性毒性试验:赋形剂组与POD-NLC组大鼠相比,各器官的脏器系数的差异无 统计学意义(P>0.05);(3)长期毒性试验:赋形剂组与POD-NLC各剂量组大鼠的一般表现、行为活动、体质量变化、血常规、血生 化、重要器官脏器系数及肝脏病理未见明显异常,且组间差异无统计学意义(P>0.05)。结论POD-NLC在阴道黏膜用药刺激性 较小,对机体无明显的急性及长期毒性,有较高的安全性。
Abstract:
Objective To test the acute and chronic toxicity of topical application of 0.5% podophyllotoxin-loaded nanostructured lipid carriers (POD-NLC) to the vaginal mucosa. Methods Twelve New Zealand rabbits were randomized into 3 groups and subjected to daily topical applications of normal saline (control group), 0.5% podophyllotoxin tincture (POD-T) or 0.5% POD-NLC on the vaginal mucosa for 10 consecutive days, and the pathological changes in the mucosa were graded using the Eckstein scoring system. The acute toxicity of POD-NLC was tested in 20 SD female rats, which received intravaginal administration of POD-NLC or vehicle for 3 times within 24 h; After 14 days of continuous observation, the rats were dissected for calculating the viscera coefficient. For testing the chronic toxicity of POD-NLC, 80 SD female rats were randomized into 4 groups and subjected to daily intravaginal administration of the vehicle or POD-NLC at low, moderate or high doses for 13 consecutive weeks. The rats were weighed once a week and at the end of the experiment, 2/3 of the rats from each group were sacrificed to collect blood samples, calculate the viscera coefficient, and examine the pathological changes in the liver. The remaining 1/3 rats were observed for another 2 weeks without further drug treatment and the same examinations were performed. Results In the rabbits, 0.5% POD-NLC elicited only mild irritation while POD-T caused moderate irritation of the vaginal mucosa. In the acute toxicity test, the organ coefficients were comparable between the rats treated with the vehicle and POD-NLC (P>0.05). Long-term intravaginal administration of POD-NLC did not produce significant changes in the behavior, activity, body weight, blood biochemical profiles or organ coefficient as compared with the vehicle control group (P>0.05). Conclusions Intravaginal administration of 0.5% POD-NLC causes very mild irritation without obvious acute or chronic toxicity to the vaginal mucosa in rabbits and rats.

相似文献/References:

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 ZENG Kang,ZHU Xiao-liang,LI Guo-feng,et al.Preparation of liposome podophyllotoxin chitosan film and determination the podophyllotoxin content in the film by ultraviolet spectrophotometry[J].Journal of Southern Medical University,2004,(12):419.
[5]张静,韩凯,王春慧,等.鬼臼毒素纳米脂质载体的靶向分布[J].南方医科大学学报,2016,(09):1237.

更新日期/Last Update: 1900-01-01