title: 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.
authors.affiliation: Department of Pharmaceutical Science, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Ave., Guangzhou 510515, PR China; Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, No. 1160 Shengli South Street, Yinchuan 750004, PR China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, No. 1160 Shengli South Street, Yinchuan 750004, PR China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Pharmaceutical Science, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Ave., Guangzhou 510515, PR China.
authors.forename: Gangjian
authors.initials: G
authors.lastname: Ji
authors.affiliation: Department of Pharmaceutical Science, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Ave., Guangzhou 510515, PR China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, No. 1160 Shengli South Street, Yinchuan 750004, PR China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, No. 1160 Shengli South Street, Yinchuan 750004, PR China.
authors.forename: Guidong
authors.initials: G
authors.lastname: Dai
authors.affiliation: College of Life Sciences of Northwest University, No. 229 Taibai North Road, Xian 710069, PR China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Science, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Ave., Guangzhou 510515, PR China. Electronic address: jhchen06@126.com.
authors.forename: Jianhai
authors.initials: J
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000235:genetics; D000470:Alkaloids / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D007783:Lactones / Q000008:administration & dosage / Q000737:chemistry; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008301:Maleimides / Q000008:administration & dosage / Q000737:chemistry; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry; D011091:Polyesters / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D011807:Quinolizines / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D000093842:Matrines
chemical_list: D000199:Actins; D000470:Alkaloids; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D004337:Drug Carriers; D007783:Lactones; D008301:Maleimides; D009842:Oligopeptides; D011091:Polyesters; D011092:Polyethylene Glycols; D011807:Quinolizines; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); C521904:poly(ethylene glycol)-block-poly(epsilon-caprolactone); C498862:Acta2 protein, rat; C043592:maleimide; C047981:arginyl-glycyl-aspartic acid; C037573:oxymatrine; D000093842:Matrines
keywords: Caprolactone (PubChem CID:10401); Ethylene glycol (PubChem CID:174); HSCs; Hepatic fibrosis; Maleimide (PubChem CID:10935); OM (PubChem CID:114850); Oxymatrine; Polymersomes; RGD