Abstract
BACKGROUND: The current study evaluates the free gallic acid (GA) and GA-loaded mesoporous silica nanoparticles (MSNs) antidepressant efficacy in a rat model of depression caused by reserpine. METHODS: By using a scanning electron microscope (SEM), dynamic light scattering (DLS), and zeta potential, MSNs and GA-loaded MSNs were characterized. The efficiency of encapsulation and the release of GA-loaded MSNs were also investigated. The effect of GA, either in its free form or loaded on (MSNs) on oxidative stress biomarkers and monoamine neurotransmitters levels (serotonin (5-HT), norepinephrine (NEP), and dopamine (DA)), were evaluated in these areas (cortex, hippocampus, striatum, and hypothalamus) of control, a depression model of rat, a depression model of rat treated with either free GA, MSNs or GA loaded MSNs. The forced swimming test (FST) also the open field test (OFT) were carried out to evaluate the behavioral changes in all groups. RESULTS: Reserpine caused a decrease in the time spent in motor and swimming activity besides increasing the time of immobility, as demonstrated by OFT and FST. Significantly reductions in 5-HT, NEP, and DA were obtained in the cortex, hippocampus, hypothalamus, and striatum of reserpine-treated rats. Free GA was more effective in increasing the serotonin level in the cortex, hippocampus, and hypothalamus, while GA-loaded MSNs were more effective in increasing it in the striatum. GA-loaded MSNs also increased the level of NEP in the four studied brain areas. Free GA increased dopamine levels in the cortex and striatum, whereas GA-loaded MSNs increased DA levels in the hippocampus and hypothalamus compared with the depressed untreated group. CONCLUSIONS: MSNs can be used as a drug delivery system to target GA selectively to specific brain areas.