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Preparation and Characterization of MKT-077 Nanoparticles for Treatment of Alzheimer’s Disease and Other Tauopathies

[ Vol. 2 , Issue. 4 ]

Author(s):

Umesh K. Jinwal, Aditya Grover, Malathi Narayan, Anjali Hirani and Vijaykumar Sutariya   Pages 217 - 226 ( 10 )

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.

Affiliation:

Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd., MDC 30, Tampa, FL 33612-4749, USA.



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