Effect of hepatocyte growth factor encapsulated in targeted liposomes on liver cirrhosis.
Hepatocyte growth factor (HGF) was encapsulated into sterically stabilized liposomes (SSL) in order to protect it from in vivo degradation. Cyclic Arg-Gly-Asp (RGD) peptides were combined with maleimide-[poly (ethylene glycol)]-1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (MAL-PEG-DOPE) incorporated into SSL. The average percentage of HGF encapsulated into liposomes was 32.38%, the size of liposomes was 91.56 nm and the polydispersity index was 0.164. In vivo, histological observation of the rat livers revealed that injection of RGD-SSL-HGF induced more significant remission of liver cirrhosis than injection of SSL-HGF, HGF alone, HGF plus RGD-SSL and saline. When the histological score, the collagen surface density, the hydroxyproline content and the expression of procollagen alpha1 (I) and alpha1 (III) mRNA in the liver were evaluated, all values were smallest in the RGD-SSL-HGF group. In contrast, an increase in apoptotic alpha-SMA-positive cells was noted in the RGD-SSL-HGF group. Together, this data suggests that targeted liposomes encapsulating HGF is a promising therapeutic modality in terms of promoting the remission of liver cirrhosis by promoting collagen fiber digestion, inhibiting collagen production, and promoting apoptosis of alpha-SMA-positive cells in rats with cirrhosis.
Li
Feng
F
Department of Gastroenterology, Zhongshan Hospital Affiliated to Fudan University, Shanghai, China.
Sun
Jian-Yong
JY
Wang
Ji-Yao
JY
Du
Shi-Lin
SL
Lu
Wei-Yue
WY
Liu
Min
M
Xie
Chao
C
Shi
Jian-Ying
JY
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D024042:Collagen Type I / Q000032:analysis; D000090602:Collagen Type I, alpha 1 Chain; D004337:Drug Carriers / Q000138:chemical synthesis / Q000627:therapeutic use; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D006909:Hydroxyproline / Q000032:analysis; D008081:Liposomes / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy*; D008301:Maleimides / Q000138:chemical synthesis; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000138:chemical synthesis / Q000737:chemistry; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D051381:Rats
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D004337:Drug Carriers; D008081:Liposomes; D008301:Maleimides; D009842:Oligopeptides; D010714:Phosphatidylethanolamines; C043592:maleimide; D011092:Polyethylene Glycols; D017228:Hepatocyte Growth Factor; C047981:arginyl-glycyl-aspartic acid; D006909:Hydroxyproline