Brain-targeted Tet-1 peptide-PLGA nanoparticles for berberine delivery against STZ-induced Alzheimer's disease in a rat model: Alleviation of hippocampal synaptic dysfunction, Tau pathology, and amyloidogenesis.

Autor: Saleh SR; Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt; Bio-Screening and Preclinical Trial Lab, Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt. Electronic address: samar.saleh@alexu.edu.eg., Abd-Elmegied A; Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt; Bio-Screening and Preclinical Trial Lab, Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt., Aly Madhy S; Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt. Electronic address: Somaya.mady_pg@alexu.edu.eg., Khattab SN; Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt. Electronic address: sherinekhattab@alexu.edu.eg., Sheta E; Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt. Electronic address: iman.sheta@alexmed.edu.eg., Elnozahy FY; Medical Physiology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt. Electronic address: fatma.yousry@alexmed.edu.eg., Mehanna RA; Medical Physiology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt; Center of Excellence for Research in Regenerative Medicine and Applications (CERRMA), Faculty of Medicine, Alexandria University, Alexandria, Egypt. Electronic address: radwa.mehanna@alexmed.edu.eg., Ghareeb DA; Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt; Bio-Screening and Preclinical Trial Lab, Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt. Electronic address: d.ghareeb@alexu.edu.eg., Abd-Elmonem NM; Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Jun 10; Vol. 658, pp. 124218. Date of Electronic Publication: 2024 May 09.
DOI: 10.1016/j.ijpharm.2024.124218
Abstrakt: Alzheimer's disease (AD) is an age-related neurodegenerative disorder that causes severe dementia and memory loss. Surface functionalized poly(lactic-co-glycolic acid) nanoparticles have been reported for better transport through the blood-brain barrier for AD therapy. This study investigated the improved therapeutic potential of berberine-loaded poly(lactic-co-glycolic acid)/Tet-1 peptide nanoparticles (BBR/PLGA-Tet NPs) in a rat model of sporadic AD. BBR was loaded into the PLGA-Tet conjugate. BBR/PLGA-Tet NPs were physicochemically and morphologically characterized. AD was achieved by bilateral intracerebroventricular (ICV) injection of streptozotocin (STZ). Cognitively impaired rats were divided into STZ, STZ + BBR, STZ + BBR/PLGA-Tet NPs, and STZ + PLGA-Tet NPs groups. Cognitive improvement was assessed using the Morris Water Maze. Brain acetylcholinesterase and monoamine oxidase activities, amyloid β42 (Aβ42), and brain glycemic markers were estimated. Further, hippocampal neuroplasticity (BDNF, pCREB, and pERK/ERK), Tau pathogenesis (pGSK3β/GSK3β, Cdk5, and pTau), inflammatory, and apoptotic markers were evaluated. Finally, histopathological changes were monitored. ICV-STZ injection produces AD-like pathologies evidenced by Aβ42 deposition, Tau hyperphosphorylation, impaired insulin signaling and neuroplasticity, and neuroinflammation. BBR and BBR/PLGA-Tet NPs attenuated STZ-induced hippocampal damage, enhanced cognitive performance, and reduced Aβ42, Tau phosphorylation, and proinflammatory responses. BBR/PLGA-Tet NPs restored neuroplasticity, cholinergic, and monoaminergic function, which are critical for cognition and brain function. BBR/PLGA-Tet NPs may have superior therapeutic potential in alleviating sporadic AD than free BBR due to their bioavailability, absorption, and brain uptake.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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