Acute and chronic toxicity of 0.5% podophyllotoxin-loaded nanostructured lipid carriers to vaginal mucosa in rabbits and rats.
10.12122/j.issn.1673-4254.2018.12.21
- Author:
Lishi LIU
1
;
Kai HAN
1
;
Qi WANG
1
;
Yan GAO
1
;
Jingying WANG
1
;
Kang ZENG
1
Author Information
1. Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
- Publication Type:Journal Article
- Keywords:
acute toxicity;
chronic toxicity;
condyloma acuminate;
irritation;
nanostructured lipid carrier;
podophyllotoxin
- MeSH:
Administration, Intravaginal;
Animals;
Female;
Liposomes;
Mucous Membrane;
drug effects;
Nanostructures;
toxicity;
Podophyllotoxin;
administration & dosage;
toxicity;
Rabbits;
Random Allocation;
Rats;
Vagina;
drug effects
- From:
Journal of Southern Medical University
2018;38(12):1527-1532
- CountryChina
- Language:Chinese
-
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 (>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 (>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.
