阿霉素毫微粒肝动脉灌注后在荷肝肿瘤鼠体内的分布研究

Body distribution of nanoparticle associated adriamycin after administration into the hepatic artery of hepatoma bearing rats

目的检测阿霉素毫微粒（ＮＡＤＭ）与游离阿霉素（ＦＡＤＭ）经肝动脉灌注后在荷肝肿瘤鼠体内的药物分布，并比较其差异。方法ＳＤ纯系大鼠３０只，建立Ｗ２５６移植性肝癌模型并随机分为两组，每组各１５只动物；经肝动脉以２ｍｇ／ｋｇ药物剂量分别注入ＮＡＤＭ与ＦＡＤＭ，每组于给药后１小时、５小时、１５小时各处死５只大鼠，分别提取血浆、肝、心、脾、肺、肾、肝肿瘤样品，采用反相高效液相色谱荧光检测法（ＲＰＨＰＬＣ）测定药物浓度。结果１小时、５小时、１５小时ＮＡＤＭ组大鼠肝、脾、肝肿瘤中阿霉素浓度均显著高于ＦＡＤＭ组（均为Ｐ＜０．０１），而血浆、心、肺中阿霉素浓度则显著降低（Ｐ值均＜０．０１）。肾组织中药物浓度在１小时、５小时以ＦＡＤＭ组为高（分别为Ｐ＜０．０５，Ｐ＜０．０１），但１５小时时两组间无显著性差异（Ｐ＞０．０５）。ＮＡＤＭ组中，给药后１小时、５小时以肝肿瘤药物浓度为最高（分别为２０．６４３μｇ／ｇ，８．８４１μｇ／ｇ），而１５小时以肝脏药物浓度为最高（５．０５４μｇ／ｇ）；各时间点均以心脏药物浓度为最低，其平均药物浓度值分别为０．１６３μｇ／ｇ，０．０７１μｇ／ｇ，０．０２５μｇ／ｇ。结论ＮＡＤＭ肝动脉给药后改变了?

Objective To determine the body distribution of nanoparticle associated adriamycin (NADM) and free adriamycin (FADM) after administration into the hepatic artery of hepatoma bearing rats, and compare the difference between them. Methods Walker 256 (W256) carcinosarcoma cells were implanted into the left lobe of 30 male SD rats, which were divided into two groups at random, with 15 rats for each group. NADM and FADM were injected into the hepatic artery of animals on 7th day after tumor inoculation. The dose of adriamycin in each formulation was 2mg/kg body weight, and the concentration was 1.0 mg/ml. At 1, 5, 15 h after drug administration, 5 animals in each group were sacrificed and the adriamycin concentrations in the plasma, liver, heart, spleen, lungs, kidneys, and tumor 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, spleen, tumor of rats at 1, 5, and 15 h post injection ( P <0.01), as compared to FADM, whereas the concentrations in the plasma, heart, lungs were significantly decreased ( P < 0.01). In the kidney, relatively higher drug concentration was found in rats accepting FADM after 1, 5 h ( P < 0.05, P <0.01, respectively) in comparison with those accepting NADM. However, the difference was not significant after 15 h ( P >0.05). The highest drug concentrations were found in the tumor at 1, 5 h (20.643 μg/g, 8.841 μg/g, respectively) and in the liver at 15 h (5.054 μg/g); the lowest concentrations were found in the heart at all time periods (0.163 μg/g, 0.071 μg/g, 0.025 μg/g, respectively) after administration with NADM. Conclusions The body distribution of adriamycin could be modified by its encapsulation in nanoparticles and administration via the hepatic artery; most of the drug was accumulated in the liver, spleen, and tumor, whereas the heart concentrations were reduced significantly.