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Lipoprotein imitating nanoparticles: Lecithin coating binds ApoE and mediates non-lysosomal uptake leading to transcytosis over the blood-brain barrier.
International Journal of Pharmaceutics 2020 August 28
Lipoproteins are naturally occurring nano sized transport vehicles in the human body. Therefore, lipoproteins could be applied as a drug carrier system. Additionally, several reports of apolipoprotein mediated blood-brain barrier (BBB) crossing suggest lipoprotein mimicking nanoparticles (NPs) as possible drug delivery vehicles to the brain. This could extend the therapy opportunities of various diseases of the central nervous system. A lipoprotein imitating NP system, consisting of a lecithin coated lipophilic cholesteryl oleate core with embedded fluorescent dye and adsorbed apolipoprotein E3 (ApoE) has been established using a two-step solvent injection method. Lecithin coating was proven to stabilize the NPs in isotonic saline solution and to bind ApoE in a highly efficient way. Fluorescent dye load (as model drug) and ApoE amount were varied, obtaining 100 nm sized, monodisperse NPs. The NPs' interaction with the BBB formed by primary porcine brain capillary endothelial cells (PBCEC) was investigated by fluorescence microscopy observing that ApoE mediated a lysosome bypassing uptake mechanism. Using this in vitro BBB model, ApoE concentration dependent permeation over the cell layer could be proven in both directions. An ApoE mediated transcytosis could be achieved, as it had been observed earlier for low-density lipoproteins. These results show that the newly developed NP system successfully mimics endogenous lipoproteins. An ApoE dependent penetration of the BBB was confirmed and provided an indication of apolipoprotein mediated transcytosis, avoiding lysosomal degradation.
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