Abstract
Pharmacological treatment of central nervous system (CNS) disorders is difficult, because the blood–brain barrier (BBB) restricts the penetration of many drugs into the brain. To solve this unmet therapeutic need, nanosized drug carriers are the focus of research efforts to develop drug delivery systems for the CNS. For the successful delivery of nanoparticles (NPs) to the brain, targeting ligands on their surface is necessary. Our research aim was to design a nanoscale drug delivery system for a more efficient transfer of donepezil, an anticholinergic drug in the therapy of Alzheimer’s disease across the BBB. Rhodamine B-labeled solid lipid nanoparticles with donepezil cargo were prepared and targeted with apolipoprotein E (ApoE), a ligand of BBB receptors. Nanoparticles were characterized by measurement of size, polydispersity index, zeta potential, thermal analysis, Fourier-transform infrared spectroscopy, in vitro release, and stability. Cytotoxicity of nanoparticles were investigated by metabolic assay and impedance-based cell analysis. ApoE-targeting increased the uptake of lipid nanoparticles in cultured brain endothelial cells and neurons. Furthermore, the permeability of ApoE-targeted nanoparticles across a co-culture model of the BBB was also elevated. Our data indicate that ApoE, which binds BBB receptors, can potentially be exploited for successful CNS targeting of solid lipid nanoparticles.
Highlights
Alzheimer’s disease (AD) is a chronic neurodegenerative disease that leads to cognitive decline, memory impairment, aphasia, and behavioural issues
The encapsulation efficiencies of the cargo donepezil were 93% and 86% in donepezil aqueous solution (DON)-Solid lipid nanoparticles (SLNs) and APOE-DON-SLNs, respectively, while for RhB the EE% was between 92–94%, which was very high
NPs and their proper functionalization are in the focus of research efforts to develop successful drug delivery systems for AD therapy
Summary
Alzheimer’s disease (AD) is a chronic neurodegenerative disease that leads to cognitive decline, memory impairment, aphasia, and behavioural issues. Therapeutic interventions for AD are intensively investigated, there is no approved drug formulation that is able to cure the disease [1]. There are five drugs approved by the Food and Drug Administration (FDA) for AD therapy, which provide modest benefit for cognitive symptoms [1]. These drugs do not stop or prevent the neurodegenerative process, only delay the progressive cognitive decline [1]. Several small molecular drugs (such as secretase inhibitors) and biopharmacons (such as anti-amyloid β antibodies) were found to be effective in transgenic
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