Constrcuction Of Nano Dual-drug Delivery System With High Drug Payload And Blood-brain-barrier Penetration And Its Application On The Treatment Of Alzheimer’s Disease

Alzheimer’s disease(AD)is a progressive degenerative nervous system disorder that is characterized by the decline in cognitive function and neuronal loss,and characterized by the presence of two core pathologies,neurofibrillary tangles(NFTs)and β-amyloid(Aβ)plaques.The disease is projected to affect as many as 50 million individuals in the world by 2050.However,there are presently no therapies available for Alzheimer’s disease.In our study,it’s prepared that a neuroprotective nano-scale product form(Met-Don-PC NPs)via the combination of the nano-drug delivery systems with the donepezil and metformin.The structures,compositions and chemical bonding states of the obtained films are investigated by using TEM,XRD,1H NMR,FTIR and UV-vis.Biological functions of Met-Don-PC NPs for nervous system are identified by bioinformatics analysis.Then it’s proved in vitro and in vivo that the Met-Don-PC NPs has good performance on neuroprotective effect via behavior tests,toluidine blue staining,immunofluorescence staining and westernblot.The Morris water test indicated that mice treated Met-Don-PC NPs exhibited significantly less neurological dysfunction.Meanwhile Met-Don-PC NPs could inhibit the inflammation of the scopolamine-induced amnesia in a mouse model.These result that the Met-Don-PC NPs is a potential neuroprotective drug for clinic application.