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.
Export Options
About this article
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 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Proinflammatory Activities of Leptin in Non-Autoimmune Conditions
Inflammation & Allergy - Drug Targets (Discontinued) The Role of α7 Nicotinic Acetylcholine Receptors and α7-Specific Antibodies in Neuroinflammation Related to Alzheimer Disease
Current Pharmaceutical Design Adrenomedullin Expression in Alzheimer's Brain
Current Alzheimer Research Xenobiotic and Non-Xenobiotic Interventions in the Microbiome Therapeutics
Current Drug Metabolism A Translational View of Peptide Treatment of Neurological Disorders
Current Medicinal Chemistry Challenges in the Design of Clinically Useful Brain-targeted Drug Nanocarriers
Current Medicinal Chemistry Advances in Antioxidative Therapy of Multiple Sclerosis
Current Medicinal Chemistry T-Cell Antigen Receptor Assembly and Cell Surface Expression Is Not Affected by Treatment with T-Cell Antigen Receptor-Alpha Chain Transmembrane Peptide
Protein & Peptide Letters CXCR3, CXCR5, CXCR6, and CXCR7 in Diabetes
Current Drug Targets Circumscribing the Conformational Peptide Epitope Landscape
Current Pharmaceutical Design Metallothionein I+II Expression as an Early Sign of Chronic Relapsing Experimental Autoimmune Encephalomyelitis in Rats
Current Aging Science Advances in Fish Cytokine Biology Give Clues to the Evolution of a Complex Network
Current Pharmaceutical Design PET Imaging of the Peripheral Benzodiazepine Receptor: Monitoring Disease Progression and Therapy Response in Neurodegenerative Disorders
Current Pharmaceutical Design CT and MR Imaging of the Encephalopathic Child
Current Medical Imaging Innovation in Contrast Agents for Magnetic Resonance Imaging
Current Medical Imaging <i>Nigella sativa</i> L., Supplementary Plant with Anticholinesterase Effect for Cognition Problems: A Kinetic Study
Current Aging Science The Multi-faceted Profile of Corticotropin-releasing Factor (CRF) Family of Neuropeptides and of their Receptors on the Paracrine/Local Regulation of the Inflammatory Response
Current Molecular Pharmacology An Overview of Non-Neural Sources of Calcitonin Gene-Related Peptide
Current Medicinal Chemistry OX40:OX40L Axis: Emerging Targets for Immunotherapy of Human Disease
Current Immunology Reviews (Discontinued) A Possible Role for Interleukin 37 in the Pathogenesis of Behcet's Disease
Current Molecular Medicine