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Published on: July 23, 2016
Luliconazole-Loaded Nanoliposomes as a Repurposing Strategy to Combat Memory Dysfunction in LPS-Induced Alzheimer's
Biswabhusan Biswal1, Snigdha Pattnaik1, Bhabani Sankar Satapathy2
1School of Pharmaceutical Sciences, Siksha "O" Anusandhan (Deemed to be University), Bhubaneswar, Odisha 751003, India.
Abstract:
Alzheimer's disease (AD) is a major neurodegenerative disorder with no definitive cure. Out of several proposed pathophysiology, microbial infection has recently been identified as one of the key pathogenic contributors for the development and progression of AD. In this context, the present study aims at a repurposing strategy through luliconazole (a potent imidazole derivative)-loaded optimized nanoliposomal carriers to treat AD. Optimized luliconazole-loaded nanoliposomes (LuNLs) were developed by the conventional thin-film hydration method followed by characterization in terms of FESEM, AFM, zeta potential, average size, loading %, and drug release (in vitro). The in vivo effectiveness of the LuNLs was investigated in LPS-induced AD rats. Molecular docking and simulation analysis demonstrated a favorable docking score between luliconazole and selected AD proteins. Spherical, nanosized (52.42 nm), negatively charged (-29.9 mV) LuNLs were reported showing a sustained drug release up to 24 h. An in vivo behavioral study depicted improved cognitive behavior in the LuNLs-treated group as compared to control groups. In vivo antioxidant activity in terms of SOD, MDA, and GSH inhibition by LuNLs was found comparable to that of standard formulation-treated groups, depicting the neuroprotective behavior of LuNLs. The histopathological observation of brain tissue in the LuNLs/control group further substantiated the in vivo behavioral study data. Based on the reports, luliconazole may be used as a viable, efficacious alternative for the treatment of AD, though further preclinical studies are highly warranted.
Insights
This study repurposed luliconazole-loaded nanoliposomes (LuNLs) to treat Alzheimer's disease (AD). LuNLs improved cognitive function and demonstrated neuroprotective effects in AD rat models, suggesting potential as an AD therapeutic.
Area of Science:
- Neuroscience
- Pharmacology
- Nanotechnology
Background:
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited treatment options.
- Microbial infection is increasingly recognized as a contributing factor to AD pathogenesis.
- Drug repurposing offers a promising avenue for developing novel AD therapeutics.
Purpose of the Study:
- To develop and evaluate luliconazole-loaded nanoliposomes (LuNLs) as a potential treatment for Alzheimer's disease.
- To investigate the efficacy of LuNLs in an LPS-induced rat model of AD.
- To explore the neuroprotective mechanisms of luliconazole in the context of AD.
Main Methods:
- Optimized luliconazole-loaded nanoliposomes (LuNLs) were prepared using thin-film hydration.
- Characterization included FESEM, AFM, zeta potential, size, loading efficiency, and in vitro drug release.
- In vivo studies involved LPS-induced AD rats, behavioral tests, antioxidant assays (SOD, MDA, GSH), and histopathology.
Main Results:
- LuNLs were spherical, nanosized (52.42 nm), negatively charged (-29.9 mV), and exhibited sustained release up to 24 hours.
- Molecular docking confirmed favorable interactions between luliconazole and AD-related proteins.
- In vivo studies showed improved cognitive behavior, enhanced antioxidant activity, and neuroprotection in LuNLs-treated rats.
- Histopathological analysis supported the neuroprotective effects of LuNLs.
Conclusions:
- Luliconazole, delivered via optimized nanoliposomal carriers, shows significant potential for treating Alzheimer's disease.
- LuNLs demonstrate neuroprotective and cognitive-enhancing effects in an AD rat model.
- Further preclinical investigations are warranted to confirm luliconazole's therapeutic viability for AD.
