卡铂碳包铁纳米笼壳聚糖纳米球在正常大鼠体内的靶向分布研究

 目的 观察卡铂碳包铁纳米笼壳聚糖纳米球 (C-Fe@CN-CN) 经肝动脉注射结合磁场引导下，在正常大鼠体内的组织分布情况。 方法 SD 大鼠 80 只，随机均分为卡铂组（ A 组）和 C-Fe@CN-CN 结合磁场组（ B 组）。肝动脉插管后， A 组注入卡铂溶液； B 组注入 C-Fe@CN-CN 分散液，以肝左叶为靶区，施加磁场 30 min 。分别于相应时间点采集标本，测定组织中卡铂浓度，观察 C-Fe@CN-CN 在各组织沉积情况。另将 C-Fe@CN-CN 用 ⁹⁹ Tc 标记后，观察体内放射性核素分布情况。 结果 B 组靶区肝卡铂峰浓度 (<>c_max)38.47 μg·g^-1 ，为非靶区肝（ 14.79 μg·g^-1 ）的 2.6 倍，为 A 组肝（ 4.98 μg·g^-1 ）的 7.7 倍。 48 h 时 B 组靶区肝卡铂浓度 3.11 μg·g^-1 ，为非靶区肝（ 0.35 μg·g^-1 ）的 8.9 倍， A 组肝卡铂浓度已低于检测限。 B 组肾、脾和肺 <> c _max 分别为 29.94 ， 1.54 和 1.76 μg·g^-1 ， A 组分别为 37.78 ， 2.14 和 2.34 μg·g^-1 ， 2 组差异有显著性。组织切片显示， C-Fe@CN-CN 聚集于靶区肝细胞间和肝窦中，非靶区肝内少见 C-Fe@CN-CN 的聚集， 其他 脏器内未见聚集的 C-Fe@CN-CN 。核素扫描显示，放射性核素浓集于靶区肝， 其他 脏器分布很少。 结论 C-Fe@CN-CN 在体内具有良好的磁靶向性和缓释性，能选择性聚集于磁靶区的细胞间隙，平稳释放药物，成倍提高靶区药物浓度，延长维持时间，同时显著性降低 其他 器官的药物浓度。

Targeted Biodistribution of Carboplatin-Fe@C Nanocage-Loaded Chitosan Nanoparticles in Rats

OBJECTIVE To observe the biodistribution of carboplatin-Fe@C nanocage-loaded chitosan nanoparticles (C-Fe@CN-CN) injected into hepatic artery under magnetic field in rats. METHODS Eighty normal rats were randomly divided into two groups. Abdominal exposure was carried out through a midline incision, and a cannula was inserted into the hepatic artery and fixed. Carboplatin was injected in Group A. In Group B, C-Fe@CN-CN was injected and the left liver lobe was under 5 000 Gs magnetic field as targeted region for 30 min. At 15, 30 min, 1, 3, 6, 12, 24 and 48 h after injuection respectively, the rats were sacrificed. The tissues of targeted liver, non-targeted liver, kidney, spleen, lung and heart were collected. The drug level of tissue was measured by flameless atomic absorption spectrophotometry. The tissue was stained by HE to observe the aggregation of C-Fe@CN-CN. C-Fe@CN-CN was also labeled with 99Tc, and the distribution of radioactivity in vivo was detected by ECT. RESULTS The cmax of caboplatin of targeted liver in Group B (38.47 μg·g-1) was increased by 1.6 times as that of non-targeted liver (14.79 μg·g-1), and 6.7 times as that of liver in Group A (4.98 μg·g-1). The concentration of carboplatin of targeted liver at 48 h in Group B (3.11 μg·g-1) was increased by 7.9 times as that of non-targeted liver (0.35 μg·g-1), and that in Group A was too low to be detected. The cmax of carboplatin in kidney, spleen, and lung in Group B (29.94, 1.54, 1.76 μg·g-1) were significantly lower than those in Group A (37.78, 2.14, 2.34 μg·g-1). The histology examination demonstrated that a lot of C-Fe@CN-CN was accumulated in the interval of liver cells or in the hepatic sinusoid in the magnetic field. There was no the aggregation of C-Fe@CN-CN in non-targeted region. The photograph of radioacticity also showed C-Fe@CN-CN was accumulated in the targeted liver. CONCLUSION C-Fe@CN-CN shows remarkable magnetic target and controlled release in vivo. It can be accumulated among cells in targeted region under magnetic field and slowly release drug to increase the levels of drug, prolong the active time and decrease the cmax in other organs.