Targeted Delivery of Montelukast for the Treatment of Alzheimer’s Disease

Abstract

: Alzheimer’s disease (AD) is one of the most common neurodegenerative disease, which affect 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 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, an 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.

Design of Montelukast Nanocrystalline Suspension for Parenteral Prolonged Delivery

“…10 Oral therapy is being clinically investigated as an alternative medication for Alzheimer's disease. [11][12][13][14][15] MTK is included in oral dosage forms in the amorphous state to provide rapid and profound dissolution and intestinal absorption of the hydrophobic compound (logP value of 8.4). 16 It was rapidly absorbed upon oral administration, exhibiting a maximum plasma concentration (C max ) within 3-4 h, with approximately 66% oral bioavailability in healthy subjects.…”