Nose-to-brain delivery of hesperidin nanoparticles loaded in-situ gel for neuroprotective action

Major depressive disorder (also known as depression) is a serious mental health condition that has a detrimental impact on a person's mood, thoughts, and behaviour. The presence of oxidative stress is associated with an increased risk of developing depression. A flavonoid called hesperidin (HSP) has been proven to be helpful in experimental depression because of its powerful antioxidant properties. However, due to its limited bioavailability, gastro-intestinal degradation, inadequate permeability, and low water solubility, the clinical development of HSP has been impeded. The objective of the present research was to develop HSP nanoparticles (NPs) loaded in-situ gel for nose-to-brain delivery to provide neuroprotective action.HSP NPs were prepared by nanoprecipitation technique and were tailored to the size by using ultrasonication technique. Optimisation of NPs was conducted using the central composite design. Prepared particles were analysed by Fourier transformed infrared spectroscopy (FTIR), DSC, and UV technique. Forced swim test was conducted as a behavioural assessment to gauze the neuroprotective antidepressant activity of the prepared formulation.The particle size was found to be in the range of 76.5±0.86nm to 239.2+0.31nm, zeta potential in the range of -8.37±0.6mV to 22.4±1.37mV, and entrapment efficiency in the range of 54.92±1.36% to 74.53±1.28%. Pharmacodynamic study showed formulation significantly decreased the immobility time in experimental animals.This study showed the potential of HSP NPs to be an effective neuroprotective agent.