Abstract:
Liver is an important organ that carries out major important functions including the detoxifcation of
harmful chemicals. Numerous studies have lately focused on the impact of various substances, such
as chemical pollutants and pharmaceutical drugs, on the liver. Melatonin (Mel) has been reported
for the protection against liver injury. In order to enhance Mel therapeutic benefts and prevent any
potential negative efects, Mel has to be delivered to the injured liver. Therefore, the goal of the
current investigation was to create Mel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Mel-
PLGA NPs) to alleviate carbon tetrachloride (CCL4)-induced liver damage in male Sprague Dawley
rats. The prepared Mel-PLGA NPs were physically characterized to determine its size and charge.
Moreover, Mel-PLGA NPs were examined, in vitro, to determine its antioxidant, anticoagulant, anti-
infammatory and cytotoxicity efects before being used in vivo. The efect of NPs on liver injury was
evaluated through biochemical, immunological, histopathological examination and fow cytometry
technique. Mel-PLGA NPs were smooth and spherical with no signs of aggregation and have in vitro
antioxidant, anti-infammatory and anticoagulant efects. NPs varied in size from 87 to 96 nm in
transmission electron microscope images, while their hydrodynamic diameter was 41 nm and their
zeta potential was −6 mV. Mel-PLGA NPs had encapsulation efciency (EE%) and drug loading (DL%)
of 59.9 and 12.5%, respectively. Treatment with Mel-PLGA NPs ameliorated all histopathological
changes, in liver sections, that resulted from CCL4 administration; where, liver sections of treated
groups were similar to those of healthy control GI. NPs administration were superior to free Mel
and reversed the elevated levels of liver function enzymes, infammatory cytokines and matrix
metalloproteinases to their normal levels. Moreover, liver sections of groups treated with NPs showed
negative immunostaining for nuclear factor-κB (NF-κB) and C-reactive protein indicating their anti-
infammatory behavior. Mel-PLGA NPs signifcantly protected liver from the toxicity of CCL4. The
efective dose of NPs was 5 mg/kg indicating a reduction in the required Mel dose and its associated
adverse efects.
