title: Cationic albumin-conjugated chelating agent as a novel brain drug delivery system in neurodegeneration.
abstract: The critical role of metal ions and in particular iron in oxidative stress and protein aggregation offers chelation therapy as a sensible pharmaceutical strategy in oxidative stress-induced neuronal damages. In this research, we conjugated an iron-chelating agent, deferasirox, to cationized human serum albumin molecules in order to develop a novel brain delivery system for the management of neurodegenerative disorders due to the significant role of oxidative stress-induced neuronal injury in such diseases. Cationized albumin is known to be able to transport to brain tissue via adsorptive-mediated transcytosis. The developed structures were molecularly characterized, and their conjugation ratio was determined. PC12 cell line was utilized to evaluate the neuroprotective features of these newly developed molecules in the presence of hydrogen peroxide neuronal damage and to identify the mechanisms behind the observed neuronal protection including apoptotic and autophagic pathways. Furthermore, a rat model of Alzheimer's disease was utilized to evaluate the impact of conjugated structures in vivo. Data analysis revealed that the conjugated species were able to hinder apoptotic cell death while enhancing autophagic process. The developed conjugated species were also able to attenuate amyloid beta-induced learning deficits when administered peripherally.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.|Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.|Nano Alvand Co., Avicenna Tech Park, Tehran University of Medical Sciences, Tehran, 1439955991, Iran.
authors.forename: Golnaz
authors.initials: G
authors.lastname: Kamalinia
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, 196151178, Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, 196151178, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Shaerzadeh
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.
authors.forename: Faranak
authors.initials: F
authors.lastname: Tavssolian
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.
authors.forename: Farkhondeh
authors.initials: F
authors.lastname: Chaharband
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.|Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 141556451, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sharifzadeh
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 141556451, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.|Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.
authors.forename: Rassoul
authors.initials: R
authors.lastname: Dinarvand
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001565:Benzoates / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002412:Cations / Q000737:chemistry; D000077588:Deferasirox; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D007502:Iron Chelating Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000737:chemistry*; D014230:Triazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D016229:Amyloid beta-Peptides; D001565:Benzoates; D002412:Cations; D004337:Drug Carriers; D007502:Iron Chelating Agents; D018696:Neuroprotective Agents; D012709:Serum Albumin; D014230:Triazoles; D000077588:Deferasirox
keywords: apoptosis; autophagy; beta-amyloid; cationized human serum albumin; deferasirox; metal chelation; neurodegeneration; oxidative stress