Pharmacokinetics, biodistribution and receptor mediated endocytosis of a natural Angelica sinensis polysaccharide.

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Pharmacokinetics, biodistribution and receptor mediated endocytosis of a natural Angelica sinensis polysaccharide.

Artif Cells Nanomed Biotechnol. 2018 Jan 01;:1-10

Authors: Zhang Y, Zhou T, Luo L, Cui Z, Wang N, Shu Y, Wang KP

Abstract
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, 99mTc-DTPA-ASP was synthesized and in vivo imaging was performed with single photon emission computed tomography (SPECT). It also showed a high aggregation of 99mTc-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.

PMID: 29291632 [PubMed - as supplied by publisher]

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