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Targeted delivery of the RGD-labeled biodegradable polymersomes loaded with the hydrophilic drug oxymatrine on cultured hepatic stellate cells and liver fibrosis in rats.

Abstract
Oxymatrine (OM) is an alkaloid extracted from a Chinese herb that has been found to possess an anti-hepatic fibrosis effect, although its anti-fibrotic potential is limited due to a lack of targeting specificity, a short half-life and adverse effects. Polymersomes (PM) assembled from amphiphilic block copolymers represent promising vesicles for applications that include drug delivery and surface functionalization. The aim of this study was to develop a novel drug carrier based on PM modified with the peptide RGD and evaluate its therapeutic effect on liver fibrosis. A series of PM based on poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) were prepared and characterized. OM was loaded into PM by a pH-gradient method then the OM-loaded PM was modified with RGD peptide to obtain RGD-PM-OM. The average drug loading of RGD-PM-OM, with a size of 95 nm, was 6.8%. The targeting effects of the system were determined in cultured hepatic stellate cells (HSCs) and bile duct-ligated rats (BLD). RGD-PM-OM displayed better suppression of HSCs proliferation and significantly reduced the expression of the genes for α-SMA and collagen lα1 in cultured HSCs. Furthermore, RGD-PM-OM exhibited markedly superior anti-fibrosis activity by reducing the levels of PC-III and IV-C in serum and connective tissue deposition in BLD compared with PM-OM and OM. These results indicate that targeted RGD-PM-OM markedly attenuates the effects of hepatic fibrosis.
AuthorsJianhong Yang, Yanhui Hou, Gangjian Ji, Zhihua Song, Yanhua Liu, Guidong Dai, Yajun Zhang, Jianhai Chen
JournalEuropean journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 52 Pg. 180-90 (Feb 14 2014) ISSN: 1879-0720 [Electronic] Netherlands
PMID24296297 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier B.V. All rights reserved.
Chemical References
  • Actins
  • Alkaloids
  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Drug Carriers
  • Lactones
  • Maleimides
  • Oligopeptides
  • Polyesters
  • Quinolizines
  • methoxy poly(ethylene glycol-co-epsilon-caprolactone)
  • poly(ethylene glycol)-block-poly(epsilon-caprolactone)
  • smooth muscle actin, rat
  • maleimide
  • Polyethylene Glycols
  • arginyl-glycyl-aspartic acid
  • oxymatrine
Topics
  • Actins (genetics)
  • Alkaloids (administration & dosage, chemistry)
  • Animals
  • Cells, Cultured
  • Collagen Type I (genetics)
  • Collagen Type I, alpha 1 Chain
  • Drug Carriers (administration & dosage, chemistry)
  • Gene Expression (drug effects)
  • Hepatic Stellate Cells (drug effects, metabolism)
  • Hydrophobic and Hydrophilic Interactions
  • Lactones (administration & dosage, chemistry)
  • Liver (drug effects, pathology)
  • Liver Cirrhosis (drug therapy, pathology)
  • Male
  • Maleimides (administration & dosage, chemistry)
  • Nanostructures (administration & dosage, chemistry)
  • Oligopeptides (administration & dosage, chemistry)
  • Polyesters (administration & dosage, chemistry)
  • Polyethylene Glycols (administration & dosage, chemistry)
  • Quinolizines (administration & dosage, chemistry)
  • Rats
  • Rats, Wistar

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