Study Of Acute Toxicity Of Epirubicin Polybutylcyanoa-crylate Nanopariticles For Rats

Object: To study the acute toxicity of EpirubicinPolybutylcyanoa-crylate Nanopariticles (EPI-PBCA-NP) for rats byinjected in vein. Research its LD₅₀, comparing it with EPI throughobserving the changes of biochemistry and peripheral blood cells and thepathology of heart, liver, lungs, kidneys, intestine of rats.Methods: The preliminary experiments determined roughly scopeof LD₅₀ of EPI-PBCA-NP. 160 rats were divided into 16 groupsrandomly. Each team has 10 rats. 8 teams were injected correspondingdose of EPI-PBCA-NP; 6 teams were injected corresponding dose ofEpirubicin (EPI) and the remaining two teams were separately injectedasepsis water or PBCA-NP by venous route. It took at least 14 days toobserve continuously after intravenous administration. Observationindexes include general indexes, animal mortality, animal weightchange, etc. Observing the changes of biochemistry and peripheralblood cells and the pathology of heart, liver, lungs, kidneys, intestine ofrats. Then detecting median lethal dose (LD50) of EPI-PBCA-NP by theBliss method; Analysing the changes of peripheral blood cells andbiochemistry(function of the liver and kidney) of rats by the SPSS(11.5).Another 20 rats were divided into two groups, each of 10 only.Finally. observing the skin irritation and sensitization test of rats after repeatedadministration of the nanodrug.Results: The LD₅₀ Values of EPI was 11.75 mg/kg, the LD₅₀ Valuesof EPI-PBCA-NP was565.95mg/kg (correspond EPI 94.90mg/kg), andthe latter increased apparently. Compared with EPI, EPI-PBCA-NPeffectively reduced the changes of the blood biochemistry andpathological damage such as cardiotoxicity, hepatotoxicity,nephrotoxicity and gastroenterotoxicity. We observed the anaphylaxis ontwo of the 20 rats.Conclusion: EPI-PBCA-NP significantly diminishes the toxicity ofEPI in some important organs such as heart, kidney, lung, ect. It will be anew type of anticancer drug produced in quantity in the foreground. EPI-PBCA-NP with some different ranges of diameters has the better livertargeting, and the characteristics of low releasing, which decreases themedicine distribution in the heart and other tissues. So it's a goodmedicine-diverting system for treating liver cancers.