Abstract
Objective: The purpose of this research work is to enhance bioavailability and brain delivery of ginger through the development of ginger-loaded chitosan nanoparticles and evaluation of its neuroprotective potential against 3-Nitropropionic acid (3-NP) induced Huntington’s Disease model rats. Methods: Ginger-loaded chitosan nanoparticles were developed as five different formulations (F1-F5) by the ionic gelation method. Based on their release, formulations F1 and F3 were chosen for physicochemical characterization. The neuroprotective activity of formulations F1 and F3 were evaluated by behavioural (Neurological scoring, Hanging wire test, Elevated plus maze test), biochemical (estimation of lipid peroxidation, glutathione, protein, superoxide dismutase, catalase) and neurochemical (estimation of acetylcholine esterase inhibition) tests in comparison with ginger extract in Huntington’s Disease (HD) model rats. Results: Formulations F1 and F3 showed almost similar and significant controlled release. Formulation F1 showed spherical nanoparticles with optimum size range and negative zeta potential. The behavioural assessment revealed that there was an improvement in gait, movement, grip strength and memory in ginger-loaded chitosan nanoformulations administered to rats than ginger extract administered rats. Biochemical and neurochemical analyses also proved that ginger-loaded chitosan nanoformulations had greatly lowered the oxidative stress parameters such as malondialdehyde and protein carbonyls in comparison with ginger extract (p<0.05). The ginger nanoformulations had highly increased the activity of antioxidant enzymes such as superoxide dismutase, glutathione and catalase by reducing the formation of free radicals than ginger extract (p<0.05). The memory and cognition of ginger nanoformulations administered Wistar rats had highly improved than ginger extract administered Wistar rats (p<0.05 due to inhibition of acetylcholine esterase enzyme). Conclusion: The current study indicated that ginger-loaded chitosan nanoparticles have a superior neuroprotective effect than their extract due to their nano size, which facilitates their entry across the blood-brain barrier and eventually improves the bioavailability of ginger.
Highlights
Huntington’s disease (HD) is a rare, genetic, neurodegenerative and fatal disease
The mechanisms that account for this selective neuronal death are multifaceted and several lines of evidence suggest that mitochondrial dysfunction, overproduction of reactive oxygen species (ROS) and oxidative stress might play important roles
When chitosan solution is added to polyanionic sodium tripolyphosphate solution, complexation occurs due to oppositely charged species, chitosan undergoes ionic gelation and precipitate to form spherical particles
Summary
Huntington’s disease (HD) is a rare, genetic, neurodegenerative and fatal disease. At present only progression delaying treatment is available. HD is caused by a trinucleotide cytosineadenine-guanine (CAG) repeat expansion in the Huntington gene. HD patients present with a triad of cognitive, behavioural and motor symptoms [1]. It has a prevalence of 5 to 10 persons per 100,000 worldwide, which makes it the most common inherited neurodegenerative disorder. Reports say that the prevalence rate of HD in India could be similar to that of the European population, which translates to about 40,000 to 70,000 ill individuals. The mechanisms that account for this selective neuronal death are multifaceted and several lines of evidence suggest that mitochondrial dysfunction, overproduction of reactive oxygen species (ROS) and oxidative stress (an imbalance between pro-oxidant and antioxidant systems resulting in oxidative damage to proteins, lipids and deoxyribonucleic acid) might play important roles
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