紫杉类药物温敏纳米胶束的小鼠LD_(50)及其毒性差异

The LD_(50) and toxic defference of paclitaxel and docetaxel thermosensitive nano-micelle

目的研究紫杉醇(Pac)和多希紫杉醇(Doc)温敏纳米胶束的急性毒性作用及其在结合和未结合热疗情况下的毒性差异。方法用不同剂量Doc和Pac温敏纳米胶束对昆明鼠行尾静脉注射,每个剂量分为热疗和非热疗组,观察小鼠用药后的急性毒副反应,计算半数致死量(LD50)。分别以两种药物最大耐受剂量对相应实验组行小鼠尾静脉注射(对照组给予等剂量生理盐水),测定外周血的白细胞和血小板。结果Doc温敏纳米胶束热疗和非热疗时小鼠尾静脉注射的LD50分别为(330.94±23.58)mg/kg和(278.07±19.81)mg/kg,Pac温敏纳米胶束的LD50分别为(104.18±5.85)mg/kg和(95.50±5.10)mg/kg。Pac和Doc均可以引起外周血白细胞和血小板显著降低;而两种药物的温敏纳米胶束对外周血白细胞和血小板的影响较小,且热疗比非热疗时影响更小。结论Pac和Doc温敏纳米胶束的急性毒性和对外周血白细胞和血小板的影响小于临床上常用的Pac和Doc注射液,且热疗时的毒性更小。

Objective To study the acute toxicity of paclitaxel （Pac） and docetaxel （doc） thermosensitive nano-micelle with and without hyperthermia. Methods Various doses of thermosensitive Pac and Doc nano-micelles were injected into the Kunming mice through caudal veins with and without hyperthermia. The 50% lethal dose （LD50） was calculated. White blood cells and platelet counts of peripheral blood were observed. Results The LD50 values of the Doc thermosensitive nano-micelles in mice with and without thermotherapy were （300.94±23.58） and （278.07±19.81） mg/kg, which of the Pac （ 104.18 ± 5.85 ） and （90. 50 ± 5.10） mg/kg, respectively. Pac and Doc reduced significantly the counts of white blood cell and platelet in peripheral blood, but the thermosensitive Pac and Doc nano±micelles did not. Conclusion The acute toxicity and side effects of thermosensitive Pac and Doc nano-micelles are less than those of Pac and Doc injection, especially with thermotherapy.