title: Sterically stable liposomes improve the therapeutic effect of hepatic stimulator substance on fulminant hepatic failure in rats.
abstract: OBJECTIVE
  Few drugs have been confirmed to be effective for fulminant hepatic failure (FHF). The purpose of this study was to prepare sterically stable liposomes (SSL) encapsulating hepatic stimulator substance (HSS) and determine their therapeutic effect on FHF.
  
  
  METHODS
  HSS were encapsulated into SSL (HSS-SSL). FHF was induced in rats by thioacetamide (TAA) injection (400mg/kg, three times with a 24-h interval). The agents, including HSS-SSL, SSL, HSS, and sodium chloride (NS), were each injected intravenously 2h after the second and the third TAA injection.
  
  
  RESULTS
  Freshly prepared HSS-SSL had a mean size of 93.59nm and the average encapsulation efficiency was 37.20%. HSS encapsulated in SSL showed a longer half life and more potent target to injured livers than free HSS. Twenty-four hours after the third TAA-injection, the survival rate of HSS-SSL-treated rats (80%) was significantly higher than that of rats treated with NS (20%), SSL (25%), or HSS (50%). Histopathologic examination showed that there was the least necrosis and inflammation in the livers of HSS-SSL-treated rats. The incidence of stage 3 or 4 hepatic encephalopathy in HSS-SSL-treated rats was significantly lower than that in rats treated with other agents. The serum pro-inflammatory cytokine levels and hepatic lipid peroxidation levels were both markedly reduced, while hepatocyte proliferative rate was markedly increased after HSS-SSL treatment.
  
  
  CONCLUSIONS
  Encapsulation by SSL markedly improved the therapeutic effect of HSS on FHF in rats. Encapsulation by SSL may be an effective approach to enhance the therapeutic potency of drugs for FHF.
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital affiliated to Fudan University, 180 Fenglin Road, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Jian-yong
authors.initials: JY
authors.lastname: Sun
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Wei-yue
authors.initials: WY
authors.lastname: Lu
authors.forename: Ji-yao
authors.initials: JY
authors.lastname: Wang
authors.forename: Jian-ying
authors.initials: JY
authors.lastname: Shi
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins; D008081:Liposomes; D017114:Liver Failure, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D010455:Peptides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide / Q000378:metabolism / Q000633:toxicity; D014018:Tissue Distribution
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D008081:Liposomes; D010455:Peptides; C073456:hepatic stimulator substance; D013853:Thioacetamide