The present study aims to evaluate the antidepressant effect of different formulations of Thymoquinone; free Thymoquinone (TQ), Thymoquinone-loaded Chitosan nanoparticles (TQ-TPP-Cs NPs) and Thymoquinone-loaded Chitosan nanoparticles coated with polysorbate 80 (TQ-TPP-Cs NPs-PSb80) that have been prepared to avoid the low bioavailability of TQ. Rats were randomly divided into control rats, rat model of depression induced by reserpine, rat model treated with TQ, rat model treated with TQ-TPP-Cs NPs and rat model treated with TQTPP- Cs NPs-PSb80. The prepared formulationswere characterized for size, morphology, encapsulation efficiency and in vitro drug release before their use in treatment. The transmission electron microscope analysisconfirmed that TQTPP- Cs NPs and TQ-TPP-Cs NPs-PSb80 were nearly spherical, having sizes of 44±1.9 and 74.66±5.6, respectively. The mean zeta potential for TQ-TPP-Cs NPs and TQ-TPP-Cs NPs-PSb80 was 30.9±3.02 mV and 3.89±2.23 mV, respectively. The TQ encapsulation efficiencies for TQ-TPP-Cs NPs and TQ-TPP-Cs NPs-PSb80 were 75.67% ± 17.03and 85.61% ± 1.02, respectively, while the loading capacities were 14.093% ± 4.61 and 16.26% ± 1.2 for TQ-TPP-Cs NPs and TQTPP- Cs NPs-PSb80, respectively. The release of TQ from TQ-TPP-Cs NPs and TQTPP- Cs NPs-PSb80 was rapid during the first 4 hrs and was followed by a sharp decrease during the next 72 hrs. Reserpine induced a decrease in motor activity and swimming time and increased immobility time as indicated from the open field test (OFT) and forced swimming test (FST). In addition, a significant decrease in the monoamine neurotransmitters serotonin (5-HT), norepinephrine (NE) and dopamine (DA) was recorded in the cortex, hippocampus and striatum of reserpine-treated rats. The results indicate that TQ-TPP-Cs NPs loaded with polysorbate 80 was more efficient in ameliorating the behavioral and neurochemical changes induced by reserpine than TQ and TQ-TPP-Cs NPs. The present data suggest that the antidepressant efficacy of TQ could be enhanced by loading it on Chitosan nanoparticles coated with polysorbate 80.
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