Fisetin-loaded pluronic-based nanogel: Radiation synthesis for alleviating neurocognitive impairments in a rat model of alzheimer's disease via modulation of the apoptotic cascade

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 propert...

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Veröffentlicht in:International journal of biological macromolecules 2024-08, Vol.274 (Pt 2), p.133472, Article 133472
Hauptverfasser: Deghiedy, Noha M., Abdel-Naby, Doaa H., Aziz, Maha M., El-Sheikh, Marwa M.
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Sprache:eng
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Zusammenfassung: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. [Display omitted] •PLUR-PAMPS nanogels were synthesized using gamma radiation•Optimized PLUR-PAMPS formulation enhances Fisetin delivery•Co-administration of AlCl3 with D-gal-induced AD in rats•Fis-PLUR-PAMPS nanogel alleviates neurocognitive impairments associated with AD•Fis-PLUR-PAMPS modulates APP, neurotransmitter, apoptosis, inflammation, and OS
ISSN:0141-8130
1879-0003
1879-0003
DOI:10.1016/j.ijbiomac.2024.133472