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.