1. Dihydroquercetin nanoparticles nasal gel is a promising formulation for amelioration of Alzheimer's disease.
- Author
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Abou-Taleb BA, El-Hadidy WF, Masoud IM, Matar NA, and Hussein HS
- Subjects
- Animals, Male, Amyloid beta-Peptides metabolism, Neuroprotective Agents administration & dosage, Neuroprotective Agents pharmacokinetics, Neuroprotective Agents chemistry, Neuroprotective Agents pharmacology, Rats, Rats, Wistar, Disease Models, Animal, Drug Carriers chemistry, Drug Liberation, Brain metabolism, Brain drug effects, Peptide Fragments, Alzheimer Disease drug therapy, Quercetin administration & dosage, Quercetin analogs & derivatives, Quercetin pharmacology, Quercetin chemistry, Quercetin pharmacokinetics, Administration, Intranasal, Nanoparticles administration & dosage, Gels, Chitosan chemistry, Chitosan analogs & derivatives, Chitosan administration & dosage
- Abstract
Dihydroquercetin is a natural flavonoid with anti-inflammatory, antioxidant, and neuroprotective activities. Dihydroquercetin exhibits a great neuroprotector promise in Alzheimer's disorder via preventing the aggregation of amyloid-beta-peptide-Aβ(1-42). The goal of the study was to create dihydroquercetin-loaded-chitosan nanoparticles (DHQ-CS NPs) loaded to a mucoadhesive, thermosensitive in-situ gel for direct nasal administration to cure Alzheimer's disorder. Loading drug in chitosan nanoparticles and incorporation into thermosensitive gel enhanced residence time and reduced mucociliary-clearance. Different in-vitro-physicochemical-characteristics of gels and nanoparticles-characterization were used to evaluate the formulations. The therapeutic effectiveness of DHQ-CS NPs gel was evaluated behaviorally, biochemically and histopathologically in Alzheimer's-rat-model compared to intranasal DHQ gel. The small particles-size was obtained = 235.3 nm of DHQ-CS NPs. The DHQ-CS NPs gel demonstrated a greater release rate compared to the raw DHQ gel. Additionally, the nasal-administration of the DHQ-CS NPs gel showed better In-vivo results compared to DHQ gel, through improvement of memory and learning deficits and also the exploratory behavior and new object memory in streptozotocin induced-Alzheimer rats. Biochemically, the intranasal DHQ-CS NPs gel, showed reduced both Aβ-protein formation and tau protein hyperphosphorylation, inhibition of acetylcholine esterase activity and oxidative stress in the brain with increase of total antioxidants in the brain and serum, compared to DHQ gel. Histopathologically, the DHQ-CS NPs nasal gel produced improvement in the hippocampal and cerebral cortex structures, being comparable to the normal group. Consequently, the intranasal DHQ-CS NPs loaded in-situ gel seems to be a promising therapeutic formulation for Alzheimer's disease medication., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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