Thymoquinone-Loaded Hexosomal Nanoparticles Attenuate Neuroinflammation and Improve Cognitive Function in an Alzheimer's Disease Mouse Model.

Authors

Nermin Eissa, Jana K Alwattar, Petrilla Jayaprakash, Haya Al Assaly, Roua Kharnoub, Aya Abed Altaleb, Khaloud Atif, Mohamad Rahal, Bassem Sadek

Published in

International journal of nanomedicine. Volume 21. Pages 627692. Epub Oct 14, 2026.

Abstract

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.
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.
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.
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.

PMID:
42894634
Bibliographic data and abstract were imported from PubMed on 19 Oct 2026.

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