Herbosomal nanocarriers using natural-origin surfactants: a quercetin-based strategy for Alzheimer's disease and oxidative-stress-driven neurodegeneration.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by oxidative stress, neuroinflammation, and cholinergic dysfunction. Quercetin (QUE) is a multifunctional flavonoid with potent antioxidant and anti-inflammatory effects and proven neuroprotective, anticancer, antimicrobial, and hepatoprotective potential. However, its therapeutic translation, particularly in the management of Alzheimer's disease, is severely limited by low aqueous solubility, low bioavailability, and rapid metabolism. The current study aims to develop QUE-loaded herbosomes as an advanced phytophospholipid delivery system for AD treatment, with a focus on replacing the synthetic surfactant Tween 80 with natural-origin betaine surfactants to overcome the drawbacks of poor biocompatibility and chronic toxicity associated with conventional surfactants. QUE herbosomes were developed using the thin-film hydration method and evaluated for physicochemical characteristics, stability, and in vitro release behavior. Formulation variables were optimized to obtain herbosomal systems with favorable nanoscale properties and sustained drug release. DSC and FTIR analyses confirmed successful incorporation of quercetin within the vesicular structure. Compared with QUE suspension, the optimized QUE herbosomal formulations (F5 &F6) showed significantly higher effect in aluminum chloride-induced AD as evidenced by Behavioral testing, biochemical, and Histopathological analyses. These findings suggest that the developed QUE herbosomes with natural-origin surfactants offer a safe and biocompatible alternative to synthetic surfactant herbosomes, improving therapeutic outcomes in AD and holding promise for other oxidative stress-related neurodegenerative conditions.