多柔比星纳米粒在大鼠体内的靶向性分布研究

Study on targeting distribution of nanoparticle-associated doxorubicin in the rats

目的 研究多柔比星纳米粒 (NDXRB)经肝动脉给药后在大鼠体内靶向性分布。方法 SD大鼠30只 ,随机分为两组 ,每组各 15只 ,经肝动脉按 2 mg/kg的剂量分别注入 NDXRB或 DXRB水溶液 ,于给药后的 1、5、15 h各处死 5只大鼠 ,分别提取心、肝、脾、肺、肾和血浆样品 ,以高效液相色谱法测定 DXRB的浓度。结果 15 h以内 NDXRB组大鼠肝和脾中 DXRB浓度均极显著高于 DXRB组 (P<0 .0 1) ,而血浆、心和肺中DXRB浓度极显著低于 DXRB组 (P<0 .0 1)。肾组织中 DXRB组浓度在 5 h以内显著高于 NDXRB组 (P<0 .0 5 ) ,15 h时两组间无显著性差异 (P>0 .0 5 )。各时间点均以心脏药物浓度为最低。结论 NDXRB肝动脉给药后改变了 DXRB的体内分布特征 。

AIM To study targeting distribution of nanoparticle-associated doxorubicin (NDXRB) in the rats after administration into the hepatic artery. Methods 30 male SD rats were divided into two groups at random, with 15 rats for each group. NDXRB and free doxorubicin (DXRB) were injected into the hepatic artery of animals. The dose of doxorubicin in each formulation was 2mg/kg body weight. At 1, 5, 15h after drug administration, 5 animals in each group were sacrificed and the doxorubicin concentrations in the heart, liver, spleen, lungs, kidneys and plasma were determined using a high performance liquid chromatography with fluorescence detector technique. Results NDXRB markedly increased the doxorubicin concentrations in the liver and spleen of rats during 15h after injection (P<0.01), as compared to DXRB, whereas the concentrations in the heart, lungs, plasma were significantly decreased (P<0.01). In the kidney, doxorubicin concentration was higher than DXRB group in rats during 5h after administration (P<0.05). However, the difference was not significant after 15h (P>0.05). The lowest concentrations were found in the heart at all time periods after administration with NDXRB. Conclusions The body distribution of doxorubicin could be modified by its encapsulation in nanoparticle and administration via the hepatic artery; most of the drug was accumulated in the liver and spleen whereas the heart concentrations were reduced significantly.