齐墩果酸/PLGA-TPGS纳米粒在小鼠体内的分布及肝靶向性研究

目的:研究齐墩果酸(OA)/乳酸羟基乙酸共聚物-水溶性维生素E(PLGA-TPGS)纳米粒(OPTN)在小鼠体内的分布及肝靶向性。方法:取小鼠随机分为12组,每组10只,前6组为OPTN组,后6组为OA溶液剂(OS)组,剂量均为20μg.g-1(以OA计)。采用高效液相色谱法测定480min内各组小鼠血清、肝、心、脾、肺、肾中的OA浓度,采用靶向指数(TI)、选择性指数(SI)、相对靶向效率(Re)和靶向效率(Te)全面评价OPTN对肝的靶向性。结果:OPTN组在小鼠血清、肝、心、脾、肺、肾中AUC0～480min值分别为(2820.83±1.57)、(5897.98±1.34)、(601.03±1.83)、(1189.50±1.46)、(1363.78±1.58)、(670.30±1.79)μg.min·mL-1,且肝脏的Te值均>2;OS组各组织的AUC0～480min值均1;与其他组织比较,肝脏Re值最大。结论:OPTN能提高药物在肝中的分布,具有肝主动靶向性,可提高药物疗效。

Study on the Distribution and Liver Targeting of OA-PLGA-TPGS-NPs in Mice

OBJECTIVE：To study the distribution and liver targeting of Oleanolic acid polylactic-co-glycolic acid D-α-tocopherol polyethylene glycol 1 000 succinate nanoparticles（OA-PLGA-TPGS-NPs,namely OPTN） in mice.METHODS：The mice were randomly divided into 12 groups,with 10 mice in each group.The former 6 groups were OPTN groups,and the latter 6 groups were OS groups.They were all given medicine 20 μg·g-1（by OA）.The concentration of OA in mice serum,liver,heart,spleen,lung and kidney were determined by HPLC within 480 min.The targeting of OPTN to liver was evaluated by using TI,SI,Re,Te.RESULTS：The AUC0～480 min of OPTN group in serum,liver,heart,spleen,lung and kidney were（2 820.83±1.57）,（5 897.98±1.34）,（601.03±1.83）,（1 189.50±1.46）,（1 363.78±1.58） and（670.30±1.79） μg·min·mL-1 respectively,and Te of liver was higher than 2.AUC0～480 min of OS groups were all lower than those of OPTN group,and Te of liver was smaller than 1 except for heart.TI hadn＇t been detected at 120,240,480 min and SI was smaller than 1 at 5 min,while TI and SI of liver at other time points were more than 1;Re of liver was the highest,compared with other tissues.CONCLUSION：OPTN can improve the distribution of drug in liver with active liver targeting and farther improve therapeutic efficacy.