Prevention of hepatic stellate cell activation using JQ1- and atorvastatin-loaded chitosan nanoparticles as a promising approach in therapy of liver fibrosis.
Actins
/ metabolism
Animals
Atorvastatin
/ administration & dosage
Azepines
/ administration & dosage
Carbon Tetrachloride
/ toxicity
Chitosan
/ chemistry
Disease Models, Animal
Drug Carriers
/ chemistry
Drug Evaluation, Preclinical
Drug Synergism
HEK293 Cells
Hepatic Stellate Cells
/ drug effects
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
/ administration & dosage
Liver
/ cytology
Liver Cirrhosis
/ chemically induced
Male
Mice
Nanoparticles
/ chemistry
Nuclear Proteins
/ antagonists & inhibitors
Transcription Factors
/ antagonists & inhibitors
Treatment Outcome
Triazoles
/ administration & dosage
Vitamin A
/ chemistry
Active targeting
Atorvastatin
Hepatic stellate cells
JQ1
Liver fibrosis
Targeting ligand density
Journal
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
ISSN: 1873-3441
Titre abrégé: Eur J Pharm Biopharm
Pays: Netherlands
ID NLM: 9109778
Informations de publication
Date de publication:
Jan 2019
Jan 2019
Historique:
received:
18
06
2018
revised:
09
10
2018
accepted:
20
11
2018
pubmed:
25
11
2018
medline:
23
4
2019
entrez:
25
11
2018
Statut:
ppublish
Résumé
Preventing hepatic stellate cell (HSC) activation represents a promising approach to resolve liver fibrosis. Several drugs have been reported to delay/prevent HSCs activation, however with limited clinical benefits. The latter may be in part attributed to the limited ability of such drugs in targeting more than one pathway of HSC activation. Added to that, is their inability of reaching their target cell in sufficient amounts to induce a therapeutic effect. In this work, chitosan NPs were loaded with JQ1 and atorvastatin, two drugs that have been reported to prevent HSCs activation, however via different mechanisms. NPs were then modified with different densities of retinol (Rt) for active targeting of HSCs. The NP HSCs targeting ability as a function of Rt density was assessed in vitro on primary HSCs and in vivo in carbon tetrachloride (CCl
Identifiants
pubmed: 30471341
pii: S0939-6411(18)30764-1
doi: 10.1016/j.ejpb.2018.11.018
pii:
doi:
Substances chimiques
(+)-JQ1 compound
0
Acta2 protein, mouse
0
Actins
0
Azepines
0
Brd4 protein, mouse
0
Drug Carriers
0
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
Nuclear Proteins
0
Transcription Factors
0
Triazoles
0
Vitamin A
11103-57-4
Chitosan
9012-76-4
Atorvastatin
A0JWA85V8F
Carbon Tetrachloride
CL2T97X0V0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
96-106Informations de copyright
Copyright © 2018. Published by Elsevier B.V.