Zhang Yu, Zhou Tao, Luo Li, Cui Zheng, Wang Na, Shu Yamin, Wang Kai-Ping
a Union Hospital of Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China.
b Hubei Key Laboratory of Nature Medicinal Chemistry and Resource Evaluation, Tongji Medical College of Pharmacy , Huazhong University of Science and Technology , Wuhan , China.
Artif Cells Nanomed Biotechnol. 2018;46(sup1):254-263. doi: 10.1080/21691401.2017.1421210. Epub 2018 Jan 1.
The interest in developing new drug carriers for delivery to the liver using natural polysaccharides with a high galactose content has necessitated the study of the pharmacokinetics and tissue distribution of these polysaccharides. In this paper, a new method was established for the microanalysis of Angelica sinensis polysaccharide (ASP) in biosamples. Fluorescein-labelled ASP (FA) was rapidly eliminated from the bloodstream and distributed to the liver with high specificity following intravenous injection. The analysis of the hepatocellular localization demonstrated that FA was predominantly endocytosed by the parenchymal cells, an observation consistent with the results obtained from microscopy studies. Additionally, FA showed a high affinity for asialoglycoprotein receptor-rich cells, while minimal binding of FA to asialoglycoprotein receptor-poor cells was observed. Moreover, the absorption of FA was markedly inhibited by the co-administration of neogalactosylalbumin (NGA) both in vivo and in vitro. To allow for the visualization of the systemic circulation of ASP, Tc-DTPA-ASP was synthesized and in vivo imaging was performed with single photon emission computed tomography (SPECT). It also showed a high aggregation of Tc-DTPA-ASP in liver. These results suggest that the distribution of ASP to the liver occurs via asialoglycoprotein receptor (ASGPR) mediated endocytosis and ASP could potentially be applied as a new carrier for delivering drugs to the liver.
利用高半乳糖含量的天然多糖开发用于肝脏给药的新型药物载体的研究兴趣，使得对这些多糖的药代动力学和组织分布进行研究成为必要。本文建立了一种用于生物样品中当归多糖（ASP）微量分析的新方法。静脉注射后，荧光素标记的ASP（FA）迅速从血液中清除，并以高特异性分布到肝脏。肝细胞定位分析表明，FA主要被实质细胞内吞，这一观察结果与显微镜研究结果一致。此外，FA对富含去唾液酸糖蛋白受体的细胞具有高亲和力，而观察到FA与缺乏去唾液酸糖蛋白受体的细胞的结合极少。此外，新半乳糖基白蛋白（NGA）在体内和体外共同给药均显著抑制了FA的吸收。为了可视化ASP的体循环，合成了Tc-DTPA-ASP并用单光子发射计算机断层扫描（SPECT）进行了体内成像。它还显示Tc-DTPA-ASP在肝脏中高度聚集。这些结果表明，ASP向肝脏的分布是通过去唾液酸糖蛋白受体（ASGPR）介导的内吞作用发生的，并且ASP有可能作为一种新的载体用于向肝脏递送药物。
