Preparation of hydrophilic C 60OH 10 /2-hydroxypropyl-β-cyclodextrin nanoparticles for the treatment of a liver injury induced by an overdose of acetaminophen

Abstract Stable hydrophilic C 60OH 10 nanoparticles were prepared from 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and applied to the treatment of an acetaminophen overdose induced liver Injury. C 60OH 10 nanoparticles were produced by cogrinding α-CD, β-CD, γ-CD and HP-β-CD and characterized in terms of solubility, mean particle diameter, ζ-potential and long term dispersibility in water. Hydrophilic C 60OH 10 nanoparticles with particle sizes less than 50 nm were effectively produced by cogrinding HP-β-CD with C 60OH 10 at a molar ratio of 1:3 (C 60OH 10 :CD). The resulting C 60OH 10 /HP-β-CD nanoparticles were stable in water and showed no aggregation over a 1 month period. The C 60OH 10 /CDs nanoparticles scavenged not only free radicals (DPPH and ABTS radicals) but also reactive oxygen species (O2•− and •OH). When C 60OH 10 /HP-β-CD nanoparticles were intraperitoneally administered to mice with a liver injury induced by an overdose of acetaminophen (APAP), the ALT and AST levels were markedly reduced to almost the same level as that for normal mice. Furthermore, the administration of the nanoparticles prolonged the survival rate of liver injured mice, while all of the mice that were treated with APAP died within 40 h. To reveal the mechanism responsible for liver protection by C 60OH 10 nanoparticles, GSH level, CYP2E1 expression and peroxynitrite formation in the liver were assessed. C 60OH 10 /HP-β-CD nanoparticles had no effect on CYP2E1 expression and GSH depletion, but suppressed the generation of peroxynitrite in the liver. The findings indicate that the protective effect of C 60OH 10 /HP-β-CD nanoparticles was due to the suppression of oxidative stress in mitochondria, as the result of scavenging ROS such as O2•− , NO and peroxynitrite, which act as critical mediators in the liver injuries.