Methylene blue (MB) has been shown to slow down the progression of the Alzheimer’s disease (AD) and other
tauopathies; however distribution of MB into the brain is limited due its high hydrophilicity. In this study, we aimed to
prepare novel hydrophobic glutathione coated PLGA nanoparticles to improve bioavailability of MB in the brain. Glutathione
coated poly-(lactide-co-glycolide) (PLGA-b-PEG) nanoparticles (NPs) were prepared and tested in two different
cell culture models of AD expressing microtubule associated protein tau (tau). The NPs showed a particle size averaging
136.5±4.4nm, which is suitable for the blood brain barrier (BBB) permeation. The in vitro release profile of the NPs exhibited
no initial burst release and showed sustained drug release for up to 144 hours. Interestingly, treatment of newly
formulated MB-NPs showed a potent reduction in both endogenous and over expressed tau protein levels in human neuroblastoma
SHSY-5Y cells expressing endogenous tau and transfected HeLa cells over-expressing tau protein, respectively.
Furthermore, in vitro BBB TranswellTM study showed significantly higher permeation of MB-NP compared to the
MB solution through the co culture of rat brain endothelial 4 (RBE4) and C6 astrocytoma cells (p<0.05). The proposed
MB loaded nanoparticles could provide a more effective treatment option for AD and many other related disorders.
Keywords: Alzheimer's disease, blood brain barrier, brain targeted delivery, drug delivery, Methylene blue, PLGA nanoparticles.
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