Abstract
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.
Current Drug Delivery
Title:Preparation and Characterization of Methylene blue Nanoparticles for Alzheimer's Disease and Other Tauopathies
Volume: 11 Issue: 4
Author(s): Umesh K. Jinwal, Anastasia Groshev, Juan Zhang, Aditya Grover and Vijaykumar B. Sutariya
Affiliation:
Keywords: Alzheimer's disease, blood brain barrier, brain targeted delivery, drug delivery, Methylene blue, PLGA nanoparticles.
Abstract: 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.
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Cite this article as:
Jinwal K. Umesh, Groshev Anastasia, Zhang Juan, Grover Aditya and Sutariya B. Vijaykumar, Preparation and Characterization of Methylene blue Nanoparticles for Alzheimer's Disease and Other Tauopathies, Current Drug Delivery 2014; 11 (4) . https://dx.doi.org/10.2174/1567201810666131113102037
DOI https://dx.doi.org/10.2174/1567201810666131113102037 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
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