scholarly journals Development of Novel Galactosylated PLGA Nanoparticles for Hepatocyte Targeting Using Molecular Modelling

Polymers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 94 ◽  
Author(s):  
Cláudia D. Raposo ◽  
Rita Costa ◽  
Krasimira T. Petrova ◽  
Catarina Brito ◽  
Marcus T. Scotti ◽  
...  
Keyword(s):  
Plga Nanoparticles ◽  
Carcinoma Cells ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
In Vitro Drug Release ◽  
Promising Tool ◽  
Three Phase ◽  
Cellular Carcinoma ◽  
Drug Encapsulation Efficiency

Doxorubicin-loaded PLGA nanoparticles conjugated with a new galactose-based ligand for the specific recognition by human hepatoma cellular carcinoma cells (Hep G2) were successfully produced. The new targeting compound was selected using molecular docking combined with quantum chemical calculations for modelling and comparing molecular interactions among the H1 subunit of the asialoglycoprotein receptor containing the carbohydrate recognition domain and the ligand. The ligand, bis(1-O-ethyl-β-D-galactopyranosyl)amine, was synthetized, characterized, and subsequently linked to PLGA. Unloaded (PLGA-di-GAL NP) and doxorubicin-loaded (DOX-PLGA-di-GAL NP) nanoparticles were prepared using an emulsion method and characterized. The produced DOX-PLGA-di-GAL NP are spherical in shape with a size of 258 ± 47 nm, a zeta potential of −62.3 mV, and a drug encapsulation efficiency of 83%. The in vitro drug release results obtained show a three-phase release profile. In vitro cell studies confirmed the interaction between Hep G2 cells and PLGA-di-GAL NP. Cell cytotoxicity tests showed that unloaded NP are nontoxic and that DOX-PLGA-di-GAL NP caused a decrease of around 80% in cellular viability. The strategy used in this work to design new targeting compounds represents a promising tool to develop effective hepatocyte targeting drug delivery systems and can be applied to other tissues/organs.

The Hep G2 Cell Line as a Possible Alternative to Isolated Hepatocytes in Cytotoxicity Studies

1988 ◽  
Vol 16 (1) ◽  
pp. 16-22
Author(s):  
Marina Marinovich ◽  
Jose L. Lorenzo ◽  
Liliana M. Flaminio ◽  
Agnese Granata ◽  
Corrado L. Galli
Keyword(s):  
Cell Line ◽  
Rat Hepatocytes ◽  
Prostaglandin E ◽  
Human Hepatoma ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Isolated Rat Hepatocytes ◽  
G2 Cells ◽  
Isolated Rat

The hepatotoxicity of carbon tetrachloride (CC14) was evaluated in vitro in freshly isolated rat hepatocytes and in the human hepatoma cell line, Hep G2. Toxicity was assessed by the leakage of cytosolic enzymes (lactate dehydrogenase and aspartate aminotransferase) and cell viability (trypan blue exclusion). The established human cells were less sensitive to CCl4-induced injury; higher doses of the toxic agent and longer incubation times were necessary to elicit cell damage. Micromolar concentrations of prostaglandin E2 significantly decreased enzyme leakage in both Hep G2 cells and rat hepatocytes challenged with CC14; a stable derivative of prostacyclin (ZK 36374) was ineffective. These results suggest that human hepatoma Hep G2 cells may represent a valid alternative to isolated rat hepatocytes for an initial approach to the in vitro evaluation of cell toxicity.

The EYTEX™ System and the Neutral Red Uptake Inhibition Assay in Cultured Hep G2 Cells as Alternative Methods for In Vivo Eye Irritation Following the EEC Protocol

1990 ◽  
Vol 17 (4) ◽  
pp. 325-333
Author(s):  
Paul J. Dierickx ◽  
Virginia C. Gordon
Keyword(s):  
Neutral Red ◽  
Alternative Methods ◽  
Inhibition Assay ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Eye Irritation ◽  
Uptake Inhibition ◽  
In Vitro Methods ◽  
Neutral Red Uptake

The neutral red uptake inhibition assay and the EYTEX™ system were investigated as alternative methods for the assessment of eye irritation, determined according to the EEC protocol. The 17 test chemicals used were mainly organic solvents. The xenobiotics were applied to Hep G2 cells for 24 hours at different concentrations. Neutral red uptake inhibition was then measured. The results are expressed as the NI50 value, which is the concentration of test compound required to induce a 50% reduction in neutral red uptake. The same chemicals were also tested as coded samples by the EYTEX™ test according to the manufacturer's directions. A nearly identical quantitative correlation was found for both in vitro methods with corneal opacity scores: r = 0.84 for EYTEX™ scores and r = 0.83 for log NI50, expressed in μg/ml. Whilst these correlations are certainly not perfect, it is clear that both in vitro methods can be used as valuable prescreening methods.

Synthesis and Processing of Human Serum Apolipoprotein AII in vitro and in Hep G2 Cells

1985 ◽  
Vol 366 (1) ◽  
pp. 173-180 ◽  
Author(s):  
Wilhelm STOFFEL ◽  
Rosemarie BLAU ◽  
Martin BURK
Keyword(s):  
Human Serum ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Synthesis And Processing ◽  
G2 Cells

Modelling ethanol cytotoxicity in vitro, in Hep G2 cells

1994 ◽  
Vol 27 (3) ◽  
pp. 211
Author(s):  
M.G. Neuman ◽  
N.H. Shear ◽  
C. Tiribelli
Keyword(s):  
Hep G2 ◽  
Hep G2 Cells ◽  
Ethanol Cytotoxicity ◽  
G2 Cells

scholarly journals Fukinolic Acid Derivatives and Triterpene Glycosides from Black Cohosh Inhibit CYP Isozymes, but are Not Cytotoxic to Hep-G2 Cells In Vitro

2010 ◽  
Vol 5 (2) ◽  
pp. 118-124 ◽  
Author(s):  
Yue Huang ◽  
Bei Jiang ◽  
Paiboon Nuntanakorn ◽  
Edward Kennelly ◽  
Stacy Shord ◽  
...  
Keyword(s):  
Triterpene Glycosides ◽  
Black Cohosh ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
G2 Cells ◽  
Cyp Isozymes

Role of cytokines in ethanol-induced cytotoxicity in vitro in Hep G2 cells

1998 ◽  
Vol 115 (1) ◽  
pp. 157-166 ◽  
Author(s):  
Manuela G. Neuman ◽  
Neil H. Shear ◽  
Stefano Bellentani ◽  
Claudio Tiribelli
Keyword(s):  
Hep G2 ◽  
Hep G2 Cells ◽  
G2 Cells

In Vitro Apoptosis Enhancement of Hep-G2 Cells by PLA–TPGS and PLA–PEG Block Copolymer Encapsulated Curcumin Nanoparticles

2013 ◽  
Vol 42 (3) ◽  
pp. 255-257 ◽  
Author(s):  
Ha Phuong Thu ◽  
Duong Tuan Quang ◽  
Mai Thi Thu Trang ◽  
Tran Thi Hong Ha ◽  
Nguyen Hoai Nam ◽  
...  
Keyword(s):  
Block Copolymer ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Curcumin Nanoparticles ◽  
G2 Cells

scholarly journals Estrogen Receptor β Activates the Human Retinoic Acid Receptorα -1 Promoter in Response to Tamoxifen and Other Estrogen Receptor Antagonists, but Not in Response to Estrogen

1999 ◽  
Vol 13 (3) ◽  
pp. 418-430 ◽  
Author(s):  
Aihua Zou ◽  
Keith B. Marschke ◽  
Katharine E. Arnold ◽  
Elaine M. Berger ◽  
Patrick Fitzgerald ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Retinoic Acid ◽  
Receptor Binding ◽  
Transcriptional Activation ◽  
Retinoic Acid Receptor ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Amino Terminal ◽  
G2 Cells

Abstract Human estrogen receptor-α (hERα) or -β (hERβ) transfected into Hep G2 or COS1 cells each responded to estrogen to increase transcription from an estrogen-responsive element (ERE)-driven reporter vector with similar fold induction through a classical mechanism involving direct receptor binding to DNA. ER antagonists inhibited this estrogen induction through both hERα and hERβ, although raloxifene was more potent through ERα than ERβ, and tamoxifen was more potent via ERβ than ERα. We have shown previously that estrogen stimulated the human retinoic acid receptor-α-1 (hRARα-1) promoter through nonclassical EREs by a mechanism that was ERα dependent, but that did not involve direct receptor binding to DNA. We show here that in contrast to hERα, hERβ did not induce reporter activity driven by the hRARα-1 promoter in the presence of estrogen. While hERβ did not confer estrogen responsiveness on this promoter, it did elicit transcriptional activation in the presence of 4-hydroxytamoxifen (4-OH-Tam). Additionally, this 4-OH-Tam agonist activity via ERβ was completely blocked by estrogen. Like ERα, transcriptional activation of this promoter by ERβ was not mediated by direct receptor binding to DNA. While hERα was shown to act through two estrogen-responsive sequences within the promoter, hERβ acted only at the 3′-region, through two Sp1 sites, in response to 4-OH-Tam. Other ER antagonists including raloxifene, ICI-164,384 and ICI-182,780 also acted as agonists through ERβ via the hRARα-1 promoter. Through the use of mutant and chimeric receptors, it was shown that the 4-OH-Tam activity via ERβ from the hRARα-1 promoter in Hep G2 cells required the amino-terminal region of ERβ, a region that was not necessary for estrogen-induced ERβ activity from an ERE in Hep G2 cells. Additionally, the progesterone receptor (PR) antagonist RU486 acted as a weak (IC50 >1 μm) antagonist via hERα and as a fairly potent (IC50 ∼200 nm) antagonist via hERβ from an ERE-driven reporter in cells that do not express PR. Although RU486 bound only weakly to ERα or ERβ in vitro, it did bind to ERβ in whole-cell binding assays, and therefore, it is likely metabolized to an ERβ-interacting compound in the cell. Interestingly, RU486 acted as an agonist through ERβ to stimulate the hRARα-1 promoter in Hep G2 cells. These findings may have ramifications in breast cancer treatment regimens utilizing tamoxifen or other ER antagonists and may explain some of the known estrogenic or antiestrogenic biological actions of RU486.

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