Title:Targeted Delivery of Montelukast for the Treatment of Alzheimer’s
Disease
Volume: 21
Issue: 10
Author(s): Ashok K. Datusalia*, Gurpreet Singh, Nikita Yadav, Sachin Gaun, Moumita Manik and Rakesh K. Singh
Affiliation:
- Department of Pharmacology and Toxicology - National Institute of Pharmaceutical Education and Research
(NIPER) Raebareli, India
- Department of Regulatory Toxicology - National Institute of Pharmaceutical Education
and Research (NIPER), Raebareli, India
Keywords:
Alzheimer’s Disease (AD), brain drug targeting, drug repurposing, montelukast, cysteinyl leukotrienes (CysLTs), neuroinflammation, therapeutic agents.
Abstract: Alzheimer’s Disease (AD) is one of the most common neurodegenerative diseases,
which affects millions of people worldwide. Accumulation of amyloid-β plaques and hyperphosphorylated
neurofibrillary tangles are the key mechanisms involved in the etiopathogenesis of AD,
characterized by memory loss and behavioural changes. Effective therapies targeting AD pathogenesis
are limited, making it the largest unmet clinical need. Unfortunately, the available drugs provide
symptomatic relief and primary care, with no substantial impact on the disease pathology.
However, in recent years researchers are working hard on several potential therapeutic targets to
combat disease pathogenesis, and few drugs have also reached clinical trials. In addition, drugs are
being repurposed both in the preclinical and clinical studies for the treatment of AD. For instance,
montelukast is the most commonly used leukotriene receptor antagonist for treating asthma and seasonal
allergy. Its leukotriene antagonistic action can also be beneficial for the reduction of detrimental
effects of leukotriene against neuro-inflammation, a hallmark feature of AD. The available
marketed formulations of montelukast present challenges such as poor bioavailability and reduced
uptake, reflecting the lack of effectiveness of its desired action in the CNS. While on the other side,
targeted drug delivery is a satisfactory approach to surpass the challenges associated with the therapeutic
agents. This review will discuss the enhancement of montelukast treatment efficacy and its
access to CNS by using new approaches like nano-formulation, nasal gel, solid lipid formulation,
nano-structure lipid carrier (NSLC), highlighting lessons learned to target AD pathologies and hurdles
that persist.