Abstract
The growing prevalence of Alzheimer’s disease (AD) throughout the world is one of the major health concerns in todays’ scenario. AD is a complex multifactorial neurodegenerative disease characterized by impaired cognitive abilities, senile plaques, neurofibrillary tangles, synapse and neuronal loss. Though wide range of drugs including acetylcholinesterase inhibitors, NMDA receptor antagonists have been recommended for the treatment of AD, but their limited ability to impart only symptomatic relief and constant failure of translation of therapeutic molecules to clinical trials arises a tremendous need to explore potential targets that could promisingly slow down the progression and development of AD. Alendronate, a nitrogen-containing bisphosphonate, is a FDA approved therapy for osteoporosis but it was cited in in-vivo and clinical studies to attenuate dementia, acetylcholinesterase activity and cholesterol synthesis in brain. Despite of these notions, alendronate face some challenges such as poor bioavailability, brain penetration and gastrointestinal side effects. However, the present study was designed with an aim to overcome these hurdles by developing alendronate-loaded chitosan nanoparticles (ALN-CS-NPs). The optimized and developed ALN-CS-NPs were demonstrated to acquire desired particle size (<200nm) and higher concentration in brain as compared to pure ALN. The ALN-CS-NPs were then evaluated in intracerebroventricular-streptozotocin (ICV-STZ) model of sporadic AD. Subsequently, it was observed that ALN-CS-NPs following intranasal administration for 15 days significantly altered the ICV-STZ induced cognitive functions, amyloid precursor protein, amyloid-β, GSK-3β, neuroinflammation and congophillic plaques in mice hippocampus. These encouraging outcomes support the promising role of ALN-CS-NPs in targeted brain delivery for the treatment of sporadic AD.
Published Version
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