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Study on the toxicity of solid lipid nanoparticles of rhynchophylline in rats

WANG Meng;TIAN Baocheng;TIAN Guiqin;SHANG Linlin;ZHANG Changyuan;ZHAO Yaxin;Department of Medicine,Jining No.1 People′s Hospital;College of Pharmacy,Binzhou Medical College;Department of Pharmacy,Jining Hospital for Infectious Diseases;Department of Pharmacy,Jining No.2 People′s Hospital;  
Objective To study the acute toxicity and long term toxicity of the solid lipid nanoparticles of rhynchophylline,and to compare the toxicity of the sustained-release tablets of rhynchophylline.Methods After a single intragastric administration of rhynchophylline solid lipid nanoparticles and rhynchophylline sustained-release pills,the animal toxicity and death rate were observed within 14 days and the LD50 was calculated.100 Wistar rats were randomly divided into blank control group,rhynchophylline solid lipid nanoparticles high and low dose groups,rhynchophylline sustained-release dropping pills,the low dose group,20 rats in each group.The rats were continuously fed for 12 weeks.The general state of the rats was observed every day and the weight was recorded every 2 weeks.After 12 weeks of administration,and after stopping for a period of 2 weeks,the blood index,blood biochemical index,and the ratio of body to body were calculated.Results The LD50 value of solid lipid nanoparticles of rhynchophylline was2 125.5 mg·kg~(-1).The 95%confidence interval was 2 019.2-2 231.6 mg·kg~(-1);The LD50 value of rhynchophylline sustained-release pill was 1 900.7 mg·kg~(-1).The 95% confidence interval was 1 651.8-2 167.9 mg·kg~(-1).After continuous intragastric administration for 12 weeks,rhynchophylline sustained-release pill high dose group showed a poor diet,a slow increase of body weight,ALT,AST,ALP,and the ratio of liver viscera increased.Also partial hepatic degeneration and focal necrosis were appeared.No significant change was found in the index of the rats in the dose group of solid lipid nanoparticles.Conclusion The solid lipid nanoparticles can improve the toxic reaction of uncaria to animal liver.
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