Nanoparticle mediated brain targeted delivery of gallic acid: in vivo behavioral and biochemical studies for improved antioxidant and antidepressant-like activity

Abstract

Context: Gallic acid had been reported to possess antidepressant like activity, which may be attributed to its CNS effects like increase in reduced glutathione levels, increased catalase activity and decreased malonaldehyde levels in brain.Objective: This study was designed to enhance the antidepressant-like activity of gallic acid (GA) using nanoparticulate delivery system in swiss male albino mice and to explore the possible underlying mechanisms for this activity.Methods: GA loaded chitosan nanoparticles (GANP) and corresponding tween 80 coated batch (cGANP) were formulated for brain targeting of GA and characterized for physicochemical parameters, morphology, differential scanning calorimetry and in vitro drug release. GA, GANP, cGANP (dose equivalent to GA 10 mg/kg, i.p.) and positive control drug, Fluoxetine (10 mg/kg, i.p.) were administered for successive seven days to male swiss albino mice. Then, the in vivo antidepressant-like activity was evaluated using Despair Swim Test (DST) and Tail Suspension Test (TST); along with the evaluation of MAO-A activity, reduced glutathione, malonaldehyde level, catalase and locomotor activity in mice.Keyfindings: cGANP (equivalent to 10 mg/kg, i.p.) significantly decreased immobility period of mice in DST and TST, indicating significant antidepressant-like activity. There was no significant effect on locomotor activity of the mice by GA and its nanoparticle formulations. cGANP (10 mg/kg, i.p.) significantly decreased Monoamine oxidase-A (MAO-A) activity, malondialdehyde levels, and catalase activity in mice.Conclusions: GA possess significant antidepressant like activity and ligand coated nanoparticle approach with improved brain targeting may serve as an effective approach to enhance such effect.