Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder marked by cognitive impairment and memory loss. In this study, AD was experimentally induced in rats using aluminum chloride (AlCl3) and D-galactose (D-gal). Fisetin (Fis), a natural compound with antioxidant and anti-inflammatory properties, has potential for neurodegeneration management, but its low bioavailability limits clinical applications. To address this, we synthesized and characterized Pluronic-2-Acrylamido-2-methylpropane sulfonic acid (PLUR-PAMPS) nanogels using gamma radiation and successfully loaded Fis onto them (Fis-PLUR-PAMPS). The optimal formulation exhibited minimal particle size, a highly acceptable polydispersity index, and the highest zeta-potential, enhancing stability and solubilization efficiency. Our goal was to improve Fis's bioavailability and assess its efficacy against AlCl3/D-gal-induced AD. Male albino Wistar rats were pre-treated orally with Fis (40 mg/kg) or Fis-PLUR-PAMPS for seven days, followed by a seven-day intraperitoneal injection of AlCl3 and D-gal. Behavioral assessments, histopathological analysis, and biochemical evaluation of markers related to AD pathology were conducted. Results demonstrated that Fis-PLUR-PAMPS effectively mitigated cognitive impairments and neurodegenerative signs induced by AlCl3/D-gal. These findings suggest that Fis-PLUR-PAMPS nanogels enhance Fis's bioavailability and therapeutic efficacy, offering a promising approach for AD management.
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