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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.
- Source :
-
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2014 Feb 14; Vol. 52, pp. 180-90. Date of Electronic Publication: 2013 Dec 01. - Publication Year :
- 2014
-
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.<br /> (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Subjects :
- Actins genetics
Alkaloids chemistry
Animals
Cells, Cultured
Collagen Type I genetics
Collagen Type I, alpha 1 Chain
Drug Carriers chemistry
Gene Expression drug effects
Hepatic Stellate Cells metabolism
Hydrophobic and Hydrophilic Interactions
Lactones administration & dosage
Lactones chemistry
Liver drug effects
Liver pathology
Liver Cirrhosis pathology
Male
Maleimides administration & dosage
Maleimides chemistry
Nanostructures administration & dosage
Nanostructures chemistry
Oligopeptides chemistry
Polyesters administration & dosage
Polyesters chemistry
Polyethylene Glycols administration & dosage
Polyethylene Glycols chemistry
Quinolizines chemistry
Rats
Rats, Wistar
Alkaloids administration & dosage
Drug Carriers administration & dosage
Hepatic Stellate Cells drug effects
Liver Cirrhosis drug therapy
Oligopeptides administration & dosage
Quinolizines administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0720
- Volume :
- 52
- Database :
- MEDLINE
- Journal :
- European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 24296297
- Full Text :
- https://doi.org/10.1016/j.ejps.2013.11.017