Potential therapeutic effects of naringin loaded PLGA nanoparticles for the management of Alzheimer's disease: In vitro, ex vivo and in vivo investigation

BACKGROUND: Alzheimer's disease (AD) is the most prevalent type of dementia which has been affected to more the 44 million people globally. It is distinguished by gradually deteriorating memory and other cognitive abilities that precede dementia. Present treatment of AD mainly focuses on symptomatic slowing the evolution of the disease which is associated with numerous side effects such as dizziness, tiredness, nausea, vomiting, heart attack, and stroke etc. Henceforth; there is urgent need to identify the alternative treatment for management of AD. Herbal medicines have been used from long time to treat AD. One of such leading Phyto molecule is Naringin. It showed promising results against AD but suffers from poor bioavailability and require in high dose to cross the blood brain barrier. OBJECTIVES: The main objectives of proposed work are to increase the bioavailability of naringin in brain by developing Nano-suspension and preclinical evaluation of neuroprotective effect of Naringin Nano-suspension (NNS) against Scopolamine induced Alzheimer's disease in rats. METHODS: The present study deals with the development, characterization of NNSand to evaluate neuroprotective effect of NNS. Nanoparticles of drug were formed by using PLGA polymer and optimized by using 3(2) factorial design. Optimized batch was further characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Further the effectiveness of NNS was preclinically investigated by performing AOTstudy as per OECD guideline 420. AD induced Albino Wistar Rats were treated with NNS orally for 14 days and then evaluated for parameters like Gross examination of brain, Relative brain weight determination, behavioural parameters, neuro-inflammatory parameters and immune-histology. RESULTS: Optimization was carried out to study the effect of polymer concentration and number of HPH cycles on Particle size, Poly dispersity index (PDI) and % entrapment efficiency. Desirability search approach was used to select the optimized formulation. Based on the selection criteria, batch F6 having 357.6 ± 05 nm particle size, 0.168 ± 0.04 PDI and 91 ± 2% EE was selected as optimized batch. SEM analysis showed spherical morphology and XRD confirmed the molecular dispersion. Pre-treatment with NNS showed neuroprotective activity basedon results of behavioural studies, biochemical estimation, neuroinflammatory parameters and immunohistochemistry evaluations. CONCLUSION: As NNS showed significant neuroprotective and anti-neuro-inflammatory effect, this study opens up new ways to exploit Naringin for various therapeutic and restorative purposes.