肝靶向药物米托蒽醌毫微球与米托蒽醌急性及延迟毒性的比较研究

Comparing study of acute and delayed toxicity of mitoxantrone-polybutycyanoacrylate-nanosphere and mitoxantrone

目的:比较米托蒽醌(mitoxantron,DHAQ)及其肝靶向制剂聚氰基丙烯酸正丁酯毫微球(mitoxantrone-polybutyl-cyanoacrylate-nanosphere,DHAQ-PBCA-NS)小鼠静脉注射的毒性。方法:昆明种小鼠一次性静脉注射两种制剂的药物后观察7天内的死亡率,延续观察14天、21天内的死亡情况,计算半数致死量(LD50)。此外,还观察多次用药的毒性情况。结果:DHAQ制成靶向制剂DHAQ-PBCA-NS后急性毒性和延迟毒性均有所下降,但都表现出有一定的延迟毒性,7、14、21天的LD50分别是,DHAQ:11.27±2.21、9.33±1.82、8.18±1.60 mg/kg,DHAQ-PBCA-NS:14.73±6.03、10.47±4.30、9.01±3.99 mg/kg。多次用药的LD50分别是DHAQ-PBCA-NS:4.225±0.798 mg/kg,DHAQ:3.670±0.627 mg/kg。结论:DHAQ和DHAQ-PBCA-NS均有一定的延迟毒性,但DHAQ-PBCA-NS的急性毒性和延迟毒性均低于DHAQ。

Objective： To study the acute and delayed toxicity of mitoxantron （DHAQ） and mitoxantrone-polybutylcyanoacrylatenanosphere （DHAQ-PBCA-NS）, a liver targeting delivery system. Methods： LD50 was applied to compare acute and delayed toxicity of DHAQ-PBCA-NS and DHAQ iv in mice. Results The two drugs have been delayed toxicity iv once time in mice, but the acute and delayed toxicity of DHAQ-PBCA-NS were lower than that of DHAQ. LD50 of DHAQ-PBCA-NS and DHAQ was 14. 73±6.03（7^th day）, 10. 47±4.30（14^thday） ,9.01±3.99（21^th day）mg/kg and 11.27±2. 21（7^th day）, 9. 33±1.82（142. day）, 8. 18±1.60（21^th day） mg/kg respectively. Conclusion： DHAQ and DHAQ-PBCA-NS have been delayed toxicity, however, the liver targeting delivery system of DHAQ exhibited less acute and delayed toxicity.