Reversal of acetaminophen intoxication with an N-acetylcysteine-liposome preparation.
An N-acetyl-l-cysteine (NAC)-liposome drug delivery system was assessed for its ability to reverse acetaminophen toxicity. Positively charged NAC-liposomes, as compared to neutral and negatively charged preparations, were highly effective in reversing acetaminophen-induced lethality in mice. The positively charged liposome preparation, when administered at a dose equivalent to 50 mg/kg NAC, increased the LD50 of acetaminophen from 840 to 1507 mg/kg; free NAC (50 mg/kg) did not significantly alter the LD50 (829 mg/kg). At this dose, only the liposome entrapped NAC protects against acetaminophen-induced lethality suggesting that positively charged liposomes enhance the delivery of NAC to hepatic parenchymal cells, the site of acetaminophen-induced necrosis.
D000082:Acetaminophen / Q000633:toxicity*; D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D007928:Lethal Dose 50; D008081:Liposomes / Q000008:administration & dosage*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D009336:Necrosis
D008081:Liposomes; D000082:Acetaminophen; D000111:Acetylcysteine