HPLC法测定阿霉素毫微粒经肝动脉灌注后大鼠体内的早期动态分布

Early dynamical body distribution of nanoparticle associated adriamycin after administration into the hepatic artery of rats determined with HPLC technique

目的 检测阿霉素毫微粒 (NADM)经肝动脉灌注后 ,在大鼠体内的药物分布 ,并与游离阿霉素 (FADM)相比较 .方法 以 α-聚氰基丙烯酸正丁酯为载体材料 ,制备NADM;SD纯系大鼠 2 4只 ,随机分为两组 ,每组 1 2只动物 ,经肝动脉分别注入 NADM与 FADM,药物剂量 2 mg·kg- 1 ,药物浓度 1 .0 g· L- 1 .每组于给药后 1 ,5 ,1 5 h各处死 4只大鼠 ,分别提取血浆、肝、心、脾、肺、肾样品 ,以反相高效液相色谱荧光检测法 (RP- HPL C)测定药物浓度 .结果 与FADM组相比 ,1 ,5 ,1 5 h时 NADM组大鼠肝、脾中阿霉素浓度显著增高 ,而血浆、肺、肾中阿霉素浓度降低 .心脏药物浓度给药后 1 h,5 h FADM组高于 NADM组 ,1 5 h时低于NADM组 .结论 NADM肝动脉给药后改变了阿霉素的体内分布特征 ,对肝、脾表现出明显的靶向性 ,而血、心、肺、肾中的药物分布减少 .

AIM To determine the body distribution of nanoparticle associated adriamycin (NADM) after administration into the hepatic artery of rats, and to compare it with that of free adriamycin (FADM). METHODS 24 male SD rats were divided into two groups at random, with 12 rats in each. NADM and FADM were injected into the hepatic artery of animals. The dose of adriamycin in each formulation was 2 mg·kg -1 body weight, and the concentration was 1.0 mg·mL -1 . At 1, 5, and 15 h after drug administration, 4 animals in each group were sacrificed and the adriamycin concentrations in the plasma, liver, heart, spleen, lungs, and kidneys were determined using a reverse phased high performance liquid chromatography with fluorescence detector (RP HPLC) technique. RESULTS NADM drastically increased the adriamycin concentrations in the liver and spleen of rats at 1, 5, and 15 h post injection, as compared to FADM, whereas the concentrations in the plasma, lungs, and kidneys decreased. Compared with those in NADM rats, relatively higher concentrations were found in the heart of FADM rats 1 and 5 h post injection but lower 15 h post injection. CONCLUSION The body distribution of adriamycin can be modified when it is encapsulated in nanoparticles and administered into the hepatic artery. Higher concentration of the drug is in the liver and spleen, whereas the concentration in the heart, plasma, kidneys, lungs is relatively lower.