Synthesis and evaluation of the effects of solid lipid nanoparticles of ivermectin and ivermectin on cuprizone-induced demyelination via targeting the TRPA۱/NF-kB/GFAP signaling pathway

Objective(s): Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) and its cause is unknown. Several environmental and genetic factors may have roles in the pathogenesis of MS. The synthesis of solid lipid nanoparticles (SLNs) for ivermectin (IVM) loading was performed to increase its efficiency and bioavailability and evaluate its ability in improving the behavioral and histopathological changes induced by cuprizone (CPZ) in the male C۵۷BL/۶ mice.   Materials and Methods: Four groups of ۷ adult C۵۷BL/۶ mice including control (normal diet), CPZ, IVM, and nano-IVM groups were chosen. After synthesis of nano-ivermectin, demyelination was induced by adding ۰.۲% CPZ to animal feed for ۶ weeks. IVM and nano-IVM (۱ mg/kg/day, IP) were given for the final ۱۴ days of the study. At last, behavioral tests, histochemical assays, and immunohistochemistry of TRPA۱, NF-kB p۶۵, and GFAP were done.Results: The time of immobility of mice in the IVM and nano-IVM groups was reduced compared to the CPZ group. Histopathological examination revealed demyelination in the CPZ group, which was ameliorated by IVM and nano-IVM administration. In IVM and nano-IVM groups corpus callosum levels of TRPA۱, NF-kB p۶۵, and GFAP were decreased compared to the CPZ group. In the IVM and nano-IVM groups, the levels of MBP were significantly higher than in the CPZ group. Conclusion: The results evidenced that IVM and nano-IVM administration is capable of reducing demyelination in mice.

Keywords:

Cuprizone , Demyelinating diseases , Inflammation , Ivermectin , Multiple Sclerosis , Nano-Ivermectin , Solid lipid nanoparticle , TRPA۱ cation channel