Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmaceutics

Cerebrovascular diseases are considered a well-recognized cause of dementia. Alzheimer's disease is the first reason of dementia followed by vascular dementia which represents a percentage of 15% to 20% of all dementia cases globally. Severe cognitive impairment that is caused by ischemic, hemorrhagic stroke or decrease in blood flow to the brain regions that are essential for memory, cognition, and behavior is one of the signs of vascular dementia.Vinpocetine, which is a vincamine derivative, is one of the currently available medications for the management of cerebrovascular and cerebral degenerative disorders due to its ability to enhance the cerebral circulation in the ischemic patients, to improve red blood cells deformability in stroke patients and to depict the neuroprotective impacts against the brain ischemia.Despite of the pharmacological benefits of vinpocetine, its clinical benefits are reduced due to the extremely poor oral bioavailability of the drug (~7%) as a result of its poor water solubility, the tremendously slow dissolution rate and the extensive first pass hepatic metabolism. Moreover, vinpocetine exhibits a short biological half-life which claims repeated drug administration with a three times daily dosing regimen with a consequent poor compliance of dementia patients.Intranasal delivery of the drugs has gained great interest as a brain delivery strategy by affording a path to the brain through the olfactory nerves. Nanoparticle formulations have been investigated to overwhelm the nasal transmucosal barrier and reach the olfactory area,where this approach can be beneficial to overcome the first pass hepatic effect and to decrease regional variability that is associated with oral delivery of drugs

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