Improvement of therapeutic potential N-acetylcysteine in acetaminophen hepatotoxicity by encapsulation in PEGylated nano-niosomes.

AIMS

N-Acetylcysteine (NAC) is an effective antidote for the treatment of acetaminophen (APAP) poisoning; however, due to its low stability and bioavailability, repeated dosing of NAC is needed. This study investigated the therapeutic efficacy of NAC by niosomal carriers.

MATERIALS AND METHODS

Niosomes were synthesized using surface active agents film hydration method and their physicochemical properties were characterized. In the in vivo study, in addition to control group, male rats were divided in different groups and challenged with an oral dose of APAP (2000 mg/kg); 4 h later, rats were administered normal saline, empty niosome (NIO), NAC (25 mg/kg) and NAC-loaded niosome (NAC-NIO) respectively, and sacrificed 48 h post-APAP overdose.

KEY FINDINGS

The particle size and zeta potential of NAC-NIO were 242.3 ± 18.5 nm and -23.9 ± 1.6 mV. The loading and encapsulation efficiency of niosomes were 1.22% ± 0.02% and 26.76% ± 6.02%. APAP administration leads to hepatic damage as evidenced by increases in serum hepatic enzyme levels and tissue levels of nitric oxide and lipid peroxidation as well as decreases in hepatic levels of reduced glutathione, catalase, superoxide dismutase, and glutathione peroxidase. Treatment of rats with NIO-NAC was remarkably more effective than NAC in improving biochemical changes such as serum hepatic aminotransferases. These findings were correlated well to the histopathological experiments.

SIGNIFICANCE

Our results suggest that NAC when delivered as a niosomal structure, is potentially more effective than NAC standard, in improving APAP-induced hepatotoxicity.