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目的观察卡铂碳包铁纳米笼壳聚糖微球(carboplatin-Fe@C-loaded chitosan nanoparticles,C-Fe@C-CN)结合磁场在移植性肝癌大鼠模型体内的靶向分布情况和药动学过程。方法建立移植性肝癌大鼠模型40只为A组,正中开腹行肝动脉插管,按卡铂5mg·kg-1体重注入C-Fe@C-CN的生理盐水分散液,以肿瘤组织为靶区施加0.5T磁场30min。分别在给药后0.25,0.5,1,3,6,12,24和48h各时间点,每组取5只大鼠处死,采集血浆、靶区肿瘤、非靶区肝、肾、脾和肺组织标本,石墨炉原子分光光度计测定血浆和组织中卡铂浓度,药物浓度数据用3P87药动学程序分析处理,并组织学观察C-Fe@C-CN的在各脏器分布情况。另40只健康大鼠为B组,以左肝叶为靶区,给予相同的处理作为对照。结果A组靶区肿瘤组织cmax是65.21μg·g-1,为B组靶区肝组织(38.47μg·g-1)的1.7倍。48h时A组靶区肿瘤组织药物浓度是7.27μg·g-1,为B组靶区肝组织(3.11μg·g-1)的2.3倍。A组靶区肿瘤组织AUC是906mg·h·L-1,为B组靶区肝组织(421.34mg·h·L-1)的2.2倍。2组药动学参数值相近。病理学观察显示,C-Fe@C-CN在磁场作用下聚集于肿瘤细胞间隙中,并可栓塞于部分细小动脉。非靶区肝组织内少见C-Fe@C-CN的聚集和栓塞的血管。结论C-Fe@C-CN在体内具有长循环和缓释特性,在磁场的引导下对肿瘤组织具有更强的靶向性,成倍提高肿瘤组织中的药物浓度,延长维持时间。
OBJECTIVE: To observe the targeted distribution of carboplatin-Fe @ C-loaded chitosan nanoparticles (C-Fe @ C-CN) binding magnetic fields in a rat model of transplantation hepatocellular carcinoma Dynamic process. Methods Forty rats of transplanted hepatocellular carcinoma (HCC) were randomly divided into three groups: group A, the middle hepatic artery was cannulated openly, the saline solution of C-Fe @ C-CN was injected into the body at 5 mg · kg-1 of carboplatin, 0.5T magnetic field applied to target 30min. At each time point of 0.25, 0.5, 1, 3, 6, 12, 24 and 48h after administration, 5 rats in each group were sacrificed and plasma, target area tumor, non-target area liver, kidney, spleen and lung Tissue samples and graphite furnace atomic spectrophotometer were used to determine the concentration of carboplatin in plasma and tissue. The drug concentration data were analyzed by 3P87 pharmacokinetics program. The distribution of C-Fe @ C-CN in various organs was observed histologically. Another 40 healthy rats as group B, the left liver lobe as the target area, given the same treatment as a control. Results The cmax of target tissue in group A was 65.21 μg · g-1, which was 1.7 times of that in group B (38.47 μg · g-1). At 48h, the concentration of drug in tumor target group A was 7.27μg · g-1, which was 2.3 times of the target group’s liver tissue (3.11μg · g-1). The AUC of target group in A group was 906 mg · h · L-1, which was 2.2 times of that of the target group in B group (421.34 mg · h-1). The pharmacokinetic parameters of two groups were similar. Pathological observations showed that C-Fe @ C-CN aggregated in tumor cell interspaces under magnetic field and could be embolized in some small arteries. Aggregation and embolization of blood vessels of rare C-Fe @ C-CN in non-target liver tissue. Conclusion C-Fe @ C-CN has long-cycle and slow-release properties in vivo. It has stronger targeting to tumor tissue under the guidance of magnetic field, doubling the drug concentration in tumor tissue and prolonging the maintenance time.