ApoE-Targeting Increases the Transfer of Solid Lipid Nanoparticles with Donepezil Cargo across a Culture Model of the Blood–Brain Barrier

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.

Chitosan-Coated PLGA Nanoparticles Loaded with Peganum harmala Alkaloids with Promising Antibacterial and Wound Healing Activities

“…The positive ZP values of the prepared H/CS/PLGA NPs, ranging from 2.63 up to 12.33 mV ( Table S1 ), are attributed to the positively charged amino groups found in CS, which coats the NPs. The obtained positively charged nanoparticles would be able to cross cell membranes efficiently [ 34 ]. The ANOVA analysis of this response showed that factor B significantly affected the ZP of the nanoparticles ( p < 0.0001).…”

Lipid Nanoparticles for Drug Delivery

“…Instead of taking advantage of Apo E present in blood, LNPs were directly modified with Apo E. The Apo E-modified Donepezil-loaded LNPs showed enhanced central nervous system targeting. [159] Similarly, Dal Magro et al used Apo E-derived peptide-functionalized LNPs to target BBB. [160]…”

Solid Lipid Nanoparticles (SLNs): An Advanced Drug Delivery System Targeting Brain through BBB

“…SLNs, as an advanced drug delivery approach, have been used to load the existing drugs, further improving bioavailability and therapeutic efficacy in treating AD [ 221 , 222 ]. Donepezil (an anti-Alzheimer’s drug), when tailored to ApoE-targeted and SLN-based formulations, the in vitro study findings showed that it has enhanced drug delivery with a favorable release profile in CMEC/D3 brain endothelial cells and human SH-SY5Y neuronal cells [ 223 ]. SLNs loaded with galantamine hydrobromide is one of the most potent anti-AD drugs [ 192 ].…”