摘要
目的:制备紫杉醇阳离子壳聚糖胶束(PTX-CCM),研究其在小鼠体内的组织分布并进行靶向性评价。方法:采用透析法制备紫杉醇阳离子壳聚糖胶束。昆明种小鼠分别尾静脉注射20 mg/kg的紫杉醇阳离子壳聚糖胶束和紫杉醇注射液,HPLC法测定各组织中不同时间的药物量,以各组织药动学参数(AUC、MRT)和靶向参数(Re、Ce、Te)为靶向评价指标。结果:PTX-CCM粒径约为164.2 nm,Zeta电位为+23.7 mV,载药量为26.40%,包封率为76.23%。以紫杉醇市售注射液为对照,紫杉醇阳离子壳聚糖胶束肝、脾、肺分布增加,AUC提高分别提高5.65、91.20和2.53倍,MRT分别延长1.83、8.40和1.16倍,相对摄取率(Re)、峰浓度比(Ce)均远大于1,靶向效率(Te)均远高于对照组,而心脏和肾脏的分布显著降低,AUC分别为对照组的61.00%和89.07%,cmax为对照组的52.62%和52.94%。结论:紫杉醇阳离子壳聚糖胶束具有优良的载药性能,相对于紫杉醇市售注射液,紫杉醇阳离子壳聚糖胶束肝、脾、肺靶向性大大提高,有利于该组织的肿瘤治疗,并可显著降低紫杉醇的心脏和肾脏毒性。
Aim:To prepare paclitaxeMoaded cationic chitosan micelles (PTX-CCM) and to study the biodistribution of PTX-CCM and paclitaxel injection (PTX-INJ) in mice. Methods:PTX-CCM was prepared by dialysis. PTX-CCM and PTX-INJ were administered to mice through caudal veins at a dose of 20 mg/kg. The RP-HPLC method was established to determine the PTX levels in the plasma and other tissues of mice. The tissues distribution and targeting effenciency were evaluated by pharmacokinetic parameters (AUC, MRT) and targeting parameters (Re, Ce and Te). Results:The drug loading and drug encapsulation of PTX-CCM were 26.40% and 76.23%, respectively, and the diameters and Zeta potential were 164.2 nm and + 23.7 mV, respectively. In comparison to PTX-INJ group, the AUCs of PTX in the liver, spleen and lung had risen 5.65, 91.20 and 2.53 times respectively in PTX-CCM group. Meanwhile,the MRT were 1.83,8.40 and 1.16 times of those of control group respectively. The relative exposure (Re) and ratio of maximum concentration(Ce) for PTX-CCM in these tissues were far more than 1 and targeting efficiecy(Te) was much higher than that of control group, while PTX in the heart and kidney decreased significantly and AUC were 61.00% and 89.07% of those of control group,meanwhile, Cmax were 52.62% and 52.94% of those of control group respectively. Conclusion: PTX-CCM shows excellent drug loading capabilities with a amount of cationic charges on their surface. It showed a higher targeting efficiency in the liver, spleen and lung in vivo and accumulates in the tissues for relatively longer time while the levels of PTX-CCM in the heart and kidney tissues are significantly reduced which might improve the treatment efficacy of PTX and decrease the side effects.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2006年第2期132-136,共5页
Journal of China Pharmaceutical University
基金
国家自然科学基金资助项目(No.30472105)~~
关键词
紫杉醇
阳离子壳聚糖胶束
组织分布
靶向
paclitaxel
cationic chitosan micelles
biodistribution
targeting