الفهرس 
GENERAL INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Alzheimer’s disease is one of the most common neurodegenerative disorders. The incidence of AD has increased recently due to the increase in the life expectancy. AD is a neurodegenerative disorder that is characterized by not only progressive impairment of memory and cognitive functions but also disturbances in behavior. Increased (OS) and decrease in acetylcholine (ACh) concentration are reported in the pathology of AD. To date, drugs for AD are not curative and can only stop the disease progression. Recently the possible treatment for AD suggested by the FDA involves the use of cholinesterase inhibitors such as e.g. donepezil, rivastigmine, galantamine and tacrine. Where, only donepezil is approved for all stages while others are used in mild to moderate conditions. Side effects of these drugs include nausea, vomiting, loss of appetite and increased frequency of bowel movements. Tacrine, the first cholinesterase inhibitor approved is rarely prescribed nowadays because of the possible liver damage associated with its use. Another medication used for mild to moderate AD is memantine which regulate the activity of glutamate by blocking the NMDA receptors but it’s also accompanied with headache, constipation, confusion and dizziness. Another suggested treatment is the use of antioxidants where large number of antioxidants has been used for treatment of various memory related disorders.
Back to nature is the concept of recent pharmaceutical research based on phytomedicine. Numerous medicinal plants possessing profound central nervous system effects and antioxidant activity have recently received attention to improve cognitive function in AD. Therefore, the effect of piperine (PIP) (the main active alkaloid in Piper nigrum) on memory performance and neurodegeneration in animal model of AD has been investigated. Structure activity relationship for PIP infers that polyene bond system makes it a potent antioxidant, while the presence of tertiary nitrogen like in acetylcholine can inhibit acetylcholenesterase enzyme or enhance cholinergic system in the brain. Nevertheless, oral PIP delivery is hampered by first pass effect by CYP 450 (cytochrome p 450). To circumvent pre-systemic clearance of PIP by oral delivery, IN route was proposed for PIP delivery and the use of bioactive excipients for enhancing oral delivery.
The current thesis suggested the use of CS-NP for intranasal delivery taking the advantages of chitosan being bioadhesive and biodegradable, CS also has the ability to open tight junctions to enhance the brain delivery. For oral delivery, ME and Cubs had been used. Both lipid based formulations contained bioactive excipients. These Excipients were used to enhance oral delivery and facilitate brain targeting.