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

柚皮苷负载 PLGA 纳米粒子对阿尔茨海默病治疗的潜在治疗效果:体外、离体和体内研究

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作者:Neelam L Dashputre, Umesh D Laddha, Prajakta P Darekar, Jayesh D Kadam, Surbhi B Patil, Rahul R Sable, Pavan B Udavant, Anjali B Tajanpure, Smita P Kakad, Sanjay J Kshirsagar

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

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.

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 32 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.

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