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Published on: July 26, 2011
Thymoquinone-Loaded Hexosomal Nanoparticles Attenuate Neuroinflammation and Improve Cognitive Function in an
Nermin Eissa1, Jana K Alwattar2, Petrilla Jayaprakash3
1Department of Biomedical Sciences, College of Health Sciences, Abu Dhabi University, Abu Dhabi, United Arab Emirates.
Introduction:
Alzheimer's disease (AD) involves neuroinflammation that worsens cognitive decline. Thymoquinone (TQ) has potent anti-inflammatory activity, but its therapeutic application is limited by poor solubility, stability, and systemic bioavailability, which may restrict effective brain exposure. This study developed TQ-loaded hexosomal nanoparticles (TQ-HNP) to enhance TQ delivery and therapeutic efficacy in a dizocilpine (MK-801)- induced mouse model of AD.
Methods:
TQ-HNP were prepared using glyceryl monooleate, oleic acid, and poloxamer 407, optimized to ~104 nm size, -31 mV zeta potential, and ~95% entrapment efficiency. Following intraperitoneal administration of free TQ and TQ-HNP, male C57BL/6 mice treated with dizocilpine received intraperitoneal injections of free TQ or TQ-HNP and were subsequently evaluated for cognitive function (Novel Object Recognition test), anxiety-like behavior (Open Field test), and brain levels of the pro-inflammatory cytokines IL-6, TNF-α, and IL-1β.
Results:
Dizocilpine impaired memory and increased anxiety-like behavior in assessed mice, while TQ-HNP significantly improved both outcomes compared to free TQ. TQ-HNP also reduced IL-6 in the hippocampus and cerebellum and lowered TNF-α and IL-1β in the cerebellum, confirming its anti-inflammatory efficacy.
Discussion:
TQ-HNP enhanced the brain delivery of thymoquinone, mitigated neuroinflammation, and restored cognitive function in the AD-like mouse model, supporting its potential as a nanocarrier-based therapeutic strategy for Alzheimer's disease and other neurodegenerative disorders.
