Abstract
Alzheimer’s disease is one of the most common causes of dementia and death in elderly populations. However, therapeutic intervention in Alzheimer’s disease is limited by the blood-brain barrier, which not only protects the brain by limiting the permeation of potential toxins into neural tissue but also by blocking certain drugs aimed at neurological disorders. MKT-077 is one such drug, which has shown promise in reducing Alzheimer’s disease- related pathology in cellular models but has limited brain permeation due to blockage by the blood-brain barrier. Herein, we describe the formulation and characterization of brain-targeted PEG-PLGA nanoparticles coated in 2% w/v glutathione to get higher blood-brain barrier permeation. Average nanoparticle size was found to be 230nm, suitable for intravenous administration and brain permeation. The nanoparticles showed steady, sustained release of MKT-077 in in vitro settings. Transwell in vitro blood-brain barrier model permeation studies showed the permeation of nanoparticles across the Transwell model to be greater than drug solution over 48 hours. The proposed model shows promise as a potential therapy against Alzheimer’s disease and other tauopathies.
Keywords: Alzheimer’s disease, blood-brain barrier, glutathione, MKT-077, nanoparticle, tau protein.
Pharmaceutical Nanotechnology
Title:Preparation and Characterization of MKT-077 Nanoparticles for Treatment of Alzheimer’s Disease and Other Tauopathies
Volume: 2 Issue: 4
Author(s): Umesh K. Jinwal, Aditya Grover, Malathi Narayan, Anjali Hirani and Vijaykumar Sutariya
Affiliation:
Keywords: Alzheimer’s disease, blood-brain barrier, glutathione, MKT-077, nanoparticle, tau protein.
Abstract: Alzheimer’s disease is one of the most common causes of dementia and death in elderly populations. However, therapeutic intervention in Alzheimer’s disease is limited by the blood-brain barrier, which not only protects the brain by limiting the permeation of potential toxins into neural tissue but also by blocking certain drugs aimed at neurological disorders. MKT-077 is one such drug, which has shown promise in reducing Alzheimer’s disease- related pathology in cellular models but has limited brain permeation due to blockage by the blood-brain barrier. Herein, we describe the formulation and characterization of brain-targeted PEG-PLGA nanoparticles coated in 2% w/v glutathione to get higher blood-brain barrier permeation. Average nanoparticle size was found to be 230nm, suitable for intravenous administration and brain permeation. The nanoparticles showed steady, sustained release of MKT-077 in in vitro settings. Transwell in vitro blood-brain barrier model permeation studies showed the permeation of nanoparticles across the Transwell model to be greater than drug solution over 48 hours. The proposed model shows promise as a potential therapy against Alzheimer’s disease and other tauopathies.
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Cite this article as:
K. Jinwal Umesh, Grover Aditya, Narayan Malathi, Hirani Anjali and Sutariya Vijaykumar, Preparation and Characterization of MKT-077 Nanoparticles for Treatment of Alzheimer’s Disease and Other Tauopathies, Pharmaceutical Nanotechnology 2014; 2 (4) . https://dx.doi.org/10.2174/2211738503666150328001726
DOI https://dx.doi.org/10.2174/2211738503666150328001726 |
Print ISSN 2211-7385 |
Publisher Name Bentham Science Publisher |
Online ISSN 2211-7393 |
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