PEG/Chitosan-Functionalized Thymol-loaded Span-based Nanovesicles for Enhanced Alzheimer’s Therapy: In-Vivo Evaluation in Induced Rat Model
Document Type
Article
Publication Date
4-23-2026
Abstract
The practical relevance of Thymol (THYM), one of the traditional neuroprotective phytotherapy for Alzheimer's disease (AD), has significant difficulties because of its low oral absorption and difficulty in passing BBB. To improve its efficacy and penetrability to brain, span-based nanocarriers, niosomes (NIO), were fabricated and optimized using Box-Behnken design. Three variables' effects were evaluated: HLB value of span, cholesterol molar ratio and drug concentration. The optimized formula (OF) was prepared, examined for particle size (PS), zeta potential (ZP), and entrapment efficiency (EE) and scored 296.85 ± 1.59 nm, − 41.66 ± 2.85 mV and 81.00 ± 1.63%, respectively. Optimized THYM-NIO was further surface modified by PEG/chitosan polymers to improve its targetability and efficacy for delivering THYM to brain. Modified OF formulae, PEGylated THYM-NIO (P-OF), THYM-chitosomes (CH-OF) and PEGylated THYM-chitosomes (PCH-OF), were then characterized by measuring PS, ZP, and EE% and showed excellent stability upon storage for 3 months. In vivo pharmacodynamic study was applied on AlCl3 induced Alzheimer's rat model to evaluate the efficacy of coated formulae versus uncoated OF and free THYM. Improvement of THYM brain delivery through coated and uncoated formulae was validated by enhanced cognitive functions approved by behavior tests and significant perfection of oxidative stress biomarkers (MDA, GSH, MOD, and GPx), anti-inflammatory biomarkers (TNF-α, IL-1β) and specific neuronal biomarkers (GFAP, dopamine, and Aβ) with superiority of double-coated formula (PCH-OF). Moreover, histopathological examination strengthened the preference of coated formulae over uncoated THYM-NIO. Development of PEGylated THYM-chitosomes is a promising approach to improve brain targetability and efficacy of THYM for AD management.
Recommended Citation
Gomaa, Eman; Mohamed, Shaimaa A.; Elghamry, Hanaa A.; Fahmy, Esraa M.; Abdelaty, Asmaa I.; and Megahed, Mohamed A., "PEG/Chitosan-Functionalized Thymol-loaded Span-based Nanovesicles for Enhanced Alzheimer’s Therapy: In-Vivo Evaluation in Induced Rat Model" (2026). Nanotechnology Research Centre. 219.
https://buescholar.bue.edu.eg/nanotech_research_centre/219