Cyclic Arg-Gly-Asp peptide-labeled liposomes for targeting drug therapy of hepatic fibrosis in rats

Shi Lin Du, Hong Pan, Wei Yue Lu, Jian Wang, Jian Wu, Ji Yao Wang

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Targeting hepatic stellate cells (HSCs) has been challenging due to the lack of specific receptors or motifs on the cells. The aim of the present study was to develop a HSC-specific system for improving drug delivery to HSCs. The affinity of a cyclic peptide containing Arg-Gly-Asp (cRGD) to collagen type VI receptor on HSCs was examined in both in vitro and in vivo experiments. Sterically stable liposomes (SSLs) were modified with this peptide to yield a new carrier, cRGD-SSL. The targeting efficiency of this carrier in delivering interferon (IFN)-α1b was investigated in a rat model of liver fibrosis induced by bile duct ligation (BDL). When incubating HSCs or hepatocytes with cyclic RGD peptide, the peptide was bound preferentially to activated HSCs. Biodistribution study showed that the accumulation of cRGD peptide-labeled liposomes in HSCs isolated from BDL rats was 10-fold more than unlabeled SSLs. BDL rats receiving injections of IFN-α1b entrapped in cRGD-SSL exhibited significantly reduced extent of liver fibrosis compared with BDL control rats or BDL rats treated with IFN-α1b entrapped in SSLs. Thus, cRGD-SSL is an efficient drug carrier, which selectively targets activated HSCs and improves drug therapy for liver fibrosis to a significant extent. This liposomal formulation represents a new means of targeting drug carrier for the treatment of liver fibrosis, and it may have potential clinical applications.

Original languageEnglish (US)
Pages (from-to)560-568
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume322
Issue number2
DOIs
StatePublished - Aug 2007

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Hepatic Stellate Cells
Liposomes
Fibrosis
Drug Therapy
Bile Ducts
Liver
Ligation
Liver Cirrhosis
Interferons
Drug Carriers
Collagen Type VI
Collagen Receptors
Cyclic Peptides
Peptides
cyclic arginine-glycine-aspartic acid peptide
Drug Delivery Systems
Hepatocytes
Injections

ASJC Scopus subject areas

  • Pharmacology

Cite this

Cyclic Arg-Gly-Asp peptide-labeled liposomes for targeting drug therapy of hepatic fibrosis in rats. / Du, Shi Lin; Pan, Hong; Lu, Wei Yue; Wang, Jian; Wu, Jian; Wang, Ji Yao.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 322, No. 2, 08.2007, p. 560-568.

Research output: Contribution to journalArticle

Du, Shi Lin ; Pan, Hong ; Lu, Wei Yue ; Wang, Jian ; Wu, Jian ; Wang, Ji Yao. / Cyclic Arg-Gly-Asp peptide-labeled liposomes for targeting drug therapy of hepatic fibrosis in rats. In: Journal of Pharmacology and Experimental Therapeutics. 2007 ; Vol. 322, No. 2. pp. 560-568.
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