The improving effects on hepatic fibrosis of interferon-γ liposomes targeted to hepatic stellate cells.

No satisfactory anti-fibrotic therapies have yet been applied clinically. One of the main reasons is the inability to specifically target the responsible cells to produce an available drug concentration and the side-effects. Exploiting the key role of the activated hepatic stellate cells (HSCs) in both hepatic fibrogenesis and over-expression of platelet-derived growth factor receptor- (PDGFR- ), we constructed targeted sterically stable liposomes (SSLs) modified by a cyclic peptide (pPB) with affinity for the PDGFR- to deliver interferon (IFN)- to HSCs. The pPB-SSL-IFN- showed satisfactory size distribution. In vitro pPB-SSL could be taken up by activated HSCs. The study of tissue distribution via living-body animal imaging showed that the pPB-SSL-IFN- mostly accumulated in the liver until 24 h. Furthermore, the pPB-SSL-IFN- showed more significant remission of hepatic fibrosis. In vivo the histological Ishak stage, the semiquantitative score for collagen in fibrotic liver and the serum levels of collagen type IV-C in fibrotic rats treated with pPB-SSL-IFN- were less than those treated with SSL-IFN- , IFN- and the control group. In vitro pPB-SSL-IFN- was also more effective in suppressing activated HSC proliferation and inducing apoptosis of activated HSCs. Thus the data suggest that pPB-SSL-IFN- might be a more effective anti-fibrotic agent and a new opportunity for clinical therapy of hepatic fibrosis.