Pharmacokinetics, biodistribution and receptor mediated endocytosis of a naturalAngelica sinensispolysaccharide

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

Hepatic targeting of glycyrrhetinic acid via nanomicelles based on stearic acid-modified fenugreek gum

“…Thus, the particle size was not the only critical factor contributing to liver targeting. Moreover, many studies have demonstrated that galactosylated copolymers or grafted polysaccharides containing galactose residues on the surfaces of nanoparticles could enhance the drug level in the liver via the recognition of nanoparticles by ASGP-R [17,24]. The previous cellular uptake experiment [12] and the cytotoxicity assay performed in this study also indicated that GA/FG-C 18 NMs were first internalised into HepG2 cells, followed by GA release into the cytoplasm, which inhibited the growth of cells.…”

Hypoxia responsive nano-drug delivery system based on angelica polysaccharide for liver cancer therapy

“…ASP, as one of the main polysaccharides extracted from the Angelica root, has anti-tumor and anti-inflammatory activities. At the same time, ASP has a high affinity for ASGPR and MR of hepatoma carcinoma cells (Zhang et al., 2018 ; Du et al., 2020 ), so it is expected to become a natural product for the preparation of liver-targeted carrier materials (Du et al., 2020 ). In this paper, an ASP-based nanocarrier was prepared by a self-assembling method in order to achieve liver targeting.…”

Angelica polysaccharide promotes proliferation and osteoblast differentiation of mesenchymal stem cells by regulation of long non-coding RNA H19

“…17 AP possesses wide-ranging pharmacological activities, such as improving the blood system, immune promotion, and anti-tumor action. These activities of AP might exert through affecting asialoglycoprotein receptor (ASGPR)-mediated endocytosis 18 and regulating TLR4. 19 Several studies demonstrated that Morinda officinalis polysaccharide (MOP), Astragalus polysaccharide (APS), and Polygonatum sibiricum polysaccharide (PSP) all have certain preventive and therapeutic effects on osteoporosis.…”