title: Pharmacological, toxicological and neuronal localization assessment of galantamine/chitosan complex nanoparticles in rats: future potential contribution in Alzheimer's disease management.
abstract: OBJECTIVE
  Nasal galantamine hydrobromide (GH)/chitosan complex nanoparticles (CX-NP2) could have an improved therapeutic potential for managing Alzheimer's disease (AD). The current study aimed to investigate if the complexation reaction between GH and chitosan altered the pharmacological and toxicological profiles of the parent drug; GH.
  
  
  METHODS
  The nasal administration of CX-NP2 to male Wistar rats for 12 consecutive days was compared to negative control group, and oral and nasal GH solutions treated groups in 3 mg/kg daily GH dose. Brain acetylcholinesterase (AChE) protein level and activity were assessed. The in vivo toxicity of CX-NP2 was evaluated via monitoring the clinical signs throughout the study. Histopathological examination of brain sections was performed. The intracellular localization of CX-NP2 within brain neurons was investigated using transmission electron microscopy.
  
  
  RESULTS
  GH/chitosan complexation did not negatively alter the pharmacological efficiency of GH. Intriguingly, nasal CX-NP2 exhibited a significant decrease of AChE protein level and activity in rat brains compared to the oral and nasal GH solutions. No toxicity signs or histopathological manifestations were noticed. The nanoparticles were found intracellularly in the brain neurons.
  
  
  CONCLUSIONS
  The pharmacological efficacy and in vivo safety of nasal CX-NP2 confirm their promising potential to contribute to the management of AD intranasally.
authors.affiliation: a Department of Pharmaceutics and Drug Manufacturing , Faculty of Pharmacy & Drug Manufacturing, Pharos University in Alexandria (PUA) , Alexandria , Egypt.
authors.forename: Amira S
authors.initials: AS
authors.lastname: Hanafy
authors.affiliation: a Department of Pharmaceutics and Drug Manufacturing , Faculty of Pharmacy & Drug Manufacturing, Pharos University in Alexandria (PUA) , Alexandria , Egypt.
authors.forename: Ragwa M
authors.initials: RM
authors.lastname: Farid
authors.affiliation: b Department of Pharmacology & Toxicology , Faculty of Pharmacy, Damanhour University , Damanhur , Egypt , and.
authors.forename: Maged W
authors.initials: MW
authors.lastname: Helmy
authors.affiliation: c Department of Pharmaceutics , Faculty of Pharmacy, University of Alexandria , Alexandria , Egypt.
authors.forename: Safaa S
authors.initials: SS
authors.lastname: ElGamal
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000281:Administration, Intranasal; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D048271:Chitosan / Q000008:administration & dosage* / Q000009:adverse effects; D016503:Drug Delivery Systems / Q000379:methods; D005702:Galantamine / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005702:Galantamine; D048271:Chitosan; D000110:Acetylcholinesterase
keywords: Alzheimer’s disease; chitosan nanoparticles; galantamine; in vivo toxicity; intranasal route