The liver-targeting study of the N-galactosylated chitosan in vivo and in vitro

Abstract

In order to study the liver targeting of the N-galactosylated chitosan (GC) polymer in liver, we first conjugated the lactobionic acid with chitosan (CS) to obtain the carrier of GC with different degree of substitution of lactosyl group. Western blot was performed to detect the expression levels of the asialoglycoprotein receptors (ASGPR) in the cell lines of HepG2, SMMC-7721, and HL-7702. The protein level of ASGPR was lower in HepG2 compared to HL-7702 and SMMC-7721. Although all treated by CS, viabilities of HL-7702 and HepG2 did not experience any significant drop, while viability of SMMC-7721 decreased 15% on average from control. It was the first data about the inhibitory effect of GC on the liver cells. Fluorescein isothiocyanate (FITC) labeled GC (GC-FITC) was injected intravenously into mice at a dose of 0.02 μmol/mouse. GC-FITC showed maximum liver localization at 5 min and even detectable at 48 h after injection. Further, the accumulation of GC in liver was about 5.4-fold higher than that of CS. In conclusion, GC demonstrated its higher efficacy in drug liver targeting and thus could be a more promising drug or gene carrier in future therapies.

Development of Asialoglycoprotein Receptor-Targeted Nanoparticles for Selective Delivery of Gemcitabine to Hepatocellular Carcinoma

“…Therefore, the plausible justification for the higher gemcitabine deposition in liver tissues might be due to the presence of galactose (asialoglycoprotein receptor ligands) on the nanoparticle surface, which might have provided specific and effective targeting to this organ. This observation is also in agreement with earlier reports wherein the drugloaded galactosylated chitosan nanoparticles successfully target the asialoglycoprotein receptor, which is overexpressed in HCC [23][24][25]. Reports also indicate that these galactosylated chitosan nanoparticles can enter cells through asialoglycoprotein receptor-mediated endocytosis, and show excellent efficacy in reducing tumor sizes in animal models [23][24][25].…”

“…This derivative contains galactose molecules, which are active ligands with specific liver targeting function. The prospective of galactosylated chitosan has been exploited as a liver-specific carrier to enhance the therapeutic efficacy of various drugs [23][24][25].…”

N-acetylaminogalactosyl-decorated biodegradable PLGA-TPGS copolymer nanoparticles containing emodin for the active targeting therapy of liver cancer

“…Due to the strong hydrophilic nature of D-a-tocopherol polyethylene glycol 1000 succinate (TPGS), the drugs could be more completely released to improve the permeability, enhance the absorption in vivo and reduce P-glycoprotein (P-gp)-mediated multiple drug resistance (MDR) [13,14]. Additionally, because of the good emulsification properties of TPGS, NPs prepared with it had a smaller particle size and a higher drug-loading (DL) and encapsulation efficiency (EE) [15,16]. Because ASGPR has a high specificity and is highly expressed on the surface of liver parenchymal cells, the liver-targeting delivery drugs or the genes mediated by it have become a research focus in recent years [16,17].…”

“…Additionally, because of the good emulsification properties of TPGS, NPs prepared with it had a smaller particle size and a higher drug-loading (DL) and encapsulation efficiency (EE) [15,16]. Because ASGPR has a high specificity and is highly expressed on the surface of liver parenchymal cells, the liver-targeting delivery drugs or the genes mediated by it have become a research focus in recent years [16,17]. The glycoprotein binding of Gal or GalNAc residues can be identified by the ASGPRs, and the affinity of GalNAc for ASGPRs is approximately 50 times higher than that of Gal [18,19].…”

Development of Nicotine Loaded Chitosan Nanoparticles for Lung Delivery

“…In the near future, more modified CS with encapsulated drugs or other conjugated excipients at C6 or both C2 and C6 could be prepared for more practicable pharmacotherapeutic strategies. In addition, toxicities of derivatives of CS in different human organs have not been completely understood although a lot of studies have been reported based on in vivo animal models (Archana, Dutta, & Dutta, 2013;Liang et al, 2014). However, there is no doubt that translation from animal models to humans is still difficult to achieve due to large differences of anatomical structures between animals and humans.…”