Paper Title
Ameliorative Potential of Neurotherapeutics Loaded Liposomes Against Amyloid Beta Induced Neuroinflammation in Mice: Nose to Brain a Novel Drug Delivery Approach

Abstract
Neurodegenerative disorders now a day have become an international threat as it prevails and progress very rapidly in developed and developing countries like India. Alzheimer’s disease (AD) is one of the most common causes of dementia in the world. The World Health Organization (WHO) predicts that by the year 2025, about 75% of the people with dementia aged 60 years and above will reside in developing countries. Liposomes have been predicted to be efficient for carrying therapeutic components across the BBB due to their optimized size, shape and surface coating. Nasal cavity has an advantage of easy accessibility, larger surface area, porous endothelial membrane, increased blood flow, and avoidance of the first-pass metabolism. Hesperidin is most widely available plant-derived bioflavonoid which has been known to exert a wide range of pharmacological activity such as antioxidant, anti-inflammatory, anti-hypercholesterolemic, and anti-carcinogenic properties. It has also been reported that the flavonoid hesperidin has tendency to protect neurons against various types of insults associated with many neurodegenerative diseases. Hence the main aim of the present investigation is to evaluate the ameliorative potential of liposome encapsulated neurotherapeutics on (Amyloid beta) Aβ25-35-induced neuroinflammation and oxidative stress in mice by transcribrial (intra-nasal) approach. Animals were pretreated with Liposome encapsulated hesperidin (LEHPN) for the periods of 3 weeks dose-dependently then received a single intra cerebro ventricular (i.c.v.) injection of Aβ25-35 (10µg/mouse). Cognitive behavioral changes in the mice were evaluated using step down inhibitory avoidance, object recognition test, Y-maze, hole board, elevated plus maze and water-maze tests. Brian level neurotransmitter such as dopamine, serotonin, glutamate, and metabolic enzymes like acetylcholinesterase, monoamine Oxidase B estimated by using spectrofluorometer. Pro-inflammatory cytokines such as IL6, TNF-α, IL-1 andNF-ĸ were estimated using quantitative PCR. Results obtained from the study indicate that treatment with LEHPN has significantly ameliorated the neurodegeneration induced by Aβ25-35. There was a significant increase in brain level serotonin, dopamine in treatment group when compared to Aβ-injected group. Pro-inflammatory cytokines IL-6, TNF-α, IL-1 and NF-ĸ has showed a sequential increase in amyloid induced group when compare to normal control. Treatment with LEHPN has shown remarkable decrease in the level of cytokine which justifies the ameliorative and anti-inflammatory potential of the formulation LEHPN. In conclusion neurotherapeutics loaded liposomes with targeted drug delivery advocates the novel strategy in the clinical management of AD and its complications. Keywords - Alzheimer’s disease, Amyloid beta, Liposomes, Hesperidin Intra-nasal, Cytokines, Neurotransmitter