摘要
目的紫杉醇壳聚糖聚合物胶束的制备及表面电荷对其在小鼠体内组织分布的影响。方法采用透析法分别制备紫杉醇阳离子(PTX-CCM)和阴离子(PTX-ACM)壳聚糖聚合物胶束;昆明种小鼠分别尾静脉注射20mg.kg-1的PTX-CCM和PTX-ACM,HPLC法测定各组织中不同时间的药物含量,以各组织药代动力学参数(AUC,MRT,Tm ax和Cm ax)评价其体内分布。结果PTX-CCM和PTX-ACM粒径分别为164和180 nm,zeta电位分别为+23.7和-28.0 mV,载药量分别为26.4%和34.6%(w/w),包封率分别为76.2%和89.9%。PTX-CCM和PTX-ACM肝中最大药物分布量分别达给药量的64.72%和91.84%,MRT分别为5.50和51.39 h;PTX-CCM和PTX-ACM脾中最大药物分布量达给药量的7.08%和5.16%,MRT分别为9.04和26.82 h;PTX-CCM肺部AUC和Cm ax分别为PTX-ACM的2.71和5.87倍;PTX-CCM和PTX-ACM心脏最高药物分布量仅为给药量的0.36%和0.24%,肾脏仅为给药量的0.75%和0.33%。结论PTX-CCM和PTX-ACM表面分别带正负电荷,具有优良的载药性能,两者皆显示出对肝脾的高度亲和性和滞留特性,尤以PTX-ACM更为显著;PTX-CCM较PTX-ACM具有更好的肺靶向性,但肺部滞留性相对较弱;两者在心、肾的分布均极少,可有效降低PTX对这些器官的毒副作用。
Aim To prepare paclitaxel-loaded cationic chitosan micelles （PTX-CCM） and paclitaxelloaded anionic chitosan micelles （PTX-ACM） and study the influence of surface charges on the biodistribution of paclitaxel-loaded chitosan polymeric micelles in mice. Methods PTX-CCM and PTX-ACM were prepared by dialysis method and were administered to mice by caudal vein at a dose of 20 mg ·kg^-1 body weight. The RP-HPLC method was established to determine the PTX concentrations in the plasma and other tissues of mice. The tissues distribution of PTX-CCM and PTX-ACM were evaluated by the pharmacokinetic parameters （AUC, MRT）. Results The diameter and zeta potential of PTX-CCM were 164 nm and ＋23.7 mV, while those of PTX-ACM were 180 nm and -28.0 mV, respectively. The drug loading and drug encapsulation efficiency for PTX-CCM were 26.4% （w/w） and 76.2% , while those of PTX-ACM were 34.6% （w/w） and 89.9% , respectively. The highest uptake of PTX-CCM and PTX-ACM in liver were 64.72% and 91.84% of dose, respectively. Meanwhile, MRT of both were 5.50 h and 51.39 h prolonged. The highest uptake of PTX-CCM and PTX-ACM in spleen were 7.08% and 5. 16% of dose, respectively. Meanwhile, MRT of both were 9.04 h and 26.82 h. For PTX-CCM group, the AUC and C of PTX in the lung were 2.71 times and 5.87 times of those of PTX-ACM group respectively. While in both PTX-CCM and PTX-ACM groups, the highest uptake of PTX in the heart were only 0.36% and 0. 24% of dose, respectively and PTX in the kidney were only 0.75% and 0.33% of dose respectively. Conclusion PTX-CCM and PTX-ACM showed excellent drug loading capabilities with amount of cationic charges and anionic charges on their surface, respectively. Both PTX-CCM and PTX- ACM groups showed a higher targeting efficiency in the liver and spleen in vivo and accumulated in both tissues for relatively long time, especially in PTX-ACM group. In contrast to PTX-ACM, PTX-CCM showed a higher lung targeting efficiency in vivo while PTX-ACM had a stronger retention ability in the lung. Meanwhile in both groups the levels of PTX in the heart and kidney tissues were significantly lower which might decrease the side effects of PTX.
出处
《药学学报》
CAS
CSCD
北大核心
2006年第9期867-872,共6页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目(30472105)
关键词
紫杉醇
壳聚糖胶束
电荷
组织分布
靶向
paclitaxel
chitosan micelle
charge
biodistribution
targeting
