Dissertation > Medicine, health > Pharmacy > Pharmacy > Pharmaceutics

The Security Study of DOX-nanoliposome

Author ZhouYanQin
Tutor ChenYuXiang
School Central South University
Course Pharmacy
Keywords DOX-nanoliposome LD50 acute toxicity chronic toxicity reproduction toxicity
CLC R943
Type Master's thesis
Year 2011
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Objective:We have prepared hydrochloride doxorubicin nano-liposomes (DOX-Lip). To evaduate the safety and lay foundation for the clinical research and use of the DOX-Lip, we have studied the acute toxicity, chronic toxicity and reproduction toxicity of the DOX-Lip.Methods:The acute toxicity was evaluated by the clinical symptom, lethal doses 50(LD50) and organic tissue pathomorphism of mice gived different doses of DOX-Lip. After giving different doses of DOX-Lip, chronic toxicity of DOX-Lip was evaluated by observing the clinical symptom and organic tissue pathomorphism of mice, and measuring blood cells, biochemical indicator and the distribution of DOX-Lip of mice in vivo. To evaluate the reproduction toxicity of DOX-Lip, micronucleus test and teratogenicity test of sperm in male mice had been done. Also, we appraisesed the influence of DOX-Lip on pregnancy and embryo of SD rats to make further evaluation of the reproduction toxicity.Results:The LD50 of the DOX-Lip is 31.69 mg/kg. The pathology result showed that, there were significant effect on heart, liver and lung with the dosage 12 mg/kg and 18 mg/kg in mice which had given 0 mg/kg,6 mg/kg,12 mg/kg and 18 mg/kg DOX-Lip respectively. The toxicity with 12 mg/kg were severer than 18 mg/kg. In the chronic toxic experiment, there were significance influence (p< 0.05) on weight, RBC hematocrit the average volume of RBC, number of PLT and percentage of eosinophil in mice with the dosage of DOX-Lip 6 mg/kg and 9 mg/kg compared with the blank control group while there was no significance Lung was damaged by DOX-Lip. DOX-Lip were mainly distributed in the liver, spleen and lung, next were the kidney and heart. The teratogenesis rate of male mice given 6 mg/kg,12 mg/kg DOX-Lip were significantly higher than 5% glucose group. Pregnant, embryo and embryo whelp of SD rats were effected by 12 mg/kg DOX-Lip.Conclusion:DOX-Lip is targetively distributed in mice. The toxicity of DOX-Lip is dose-dependent in mice. DOX-Lip is considered to have reproductive toxicity in mice. So it should be prudent when it is used in clinical.

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