Naringenin-loaded, tween 80-coated chitosan nanoparticles: a promising therapeutic for streptozotocin induced cognitive deficit in mice

The current study aimed to formulate naringenin nanoparticles (NNPs) with chitosan polymer and investigate their protective effect against cognitive deficit induced by streptozotocin (STZ) in swiss albino mice. The interactions of naringenin with the possible targets involved in the pathogenesis of cognitive deficit were predicted using AutoDock vina and predicted its absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties with SwissADME and ProTox-II web servers. NNPs were formulated with chitosan using the ionotropic gelation method and coated with tween 80. The cognition functions of NNPs were evaluated by Elevated Plus Maze (EPM) and Novel Objective Recognition test (NORT) in STZ-induced cognitive deficit in mice at doses 50 and 100 mg/kg equivalent to pure drug, i.p. The effect of NNPs on various antioxidant enzymes (glutathione, superoxide dismutase, catalase, and mitochondrial complexes (1–4)) in cortex and hippocampus region of the brain was also estimated by biochemical methods. <i>In silico</i> study revealed better binding interactions as well as good binding affinity of naringenin with all the studied targets compared to rivastigmine. The formulated coated NNPs displayed good drug entrapment efficiency (75.412%) and a good <i>in vitro</i> release that followed the Korsmeyer–Peppas model (R² = 0.962). Furthermore, <i>in-vivo</i> studies displayed a learning and memory-enhancing effect of NNPs in EPM and NORT models compared to naringenin alone. A significant increase in the level of antioxidant enzymes revealed that the protective effects of naringenin nanoformulation might be mediated by its potent antioxidant and mitochondrial restoring properties. Collectively, these studies suggested that the nanoformulation of naringenin is worthwhile for the management of cognitive improvement and other neurological problems.