Intranasal delivery of deferoxamine reduces spatial memory loss in APP/PS1 mice

Drug Delivery and Translational Research
Leah R HansonWilliam H Frey

Abstract

Intranasal administration, which bypasses the blood-brain barrier and minimizes systemic exposure, is a non-invasive alternative for targeted drug delivery to the brain. While identification of metal dysregulation in Alzheimer's brain has led to the development of therapeutic metal-binding agents, targeting to the brain has remained an issue. The purpose of this study was to both determine concentrations of deferoxamine (DFO), a high-affinity iron chelator, reaching the brains of mice after intranasal administration and to determine its efficacy in a mouse model of spatial memory loss. Intranasal administration of DFO (2.4 mg) labeled with (59)Fe (75 μCi) to C57 mice resulted in micromolar concentrations at 30 min within brain parenchyma. After 3 months of intranasal DFO treatment, 2.4 mg three times per week, 48-week-old APP/PS1 mice had significantly reduced escape latencies in Morris water maze compared to vehicle-treated mice. This is the first report that intranasal DFO improves spatial memory in a mouse model of Alzheimer's disease and demonstrates that intranasal DFO reaches the brain in therapeutic doses.

References

Jun 1, 1991·Lancet·D R Crapper McLachlanD F Andrews
May 1, 1989·The American Journal of the Medical Sciences·G S GordonJ H Githens
Jan 1, 1988·Critical Reviews in Clinical Laboratory Sciences·C Hershko, D J Weatherall
Oct 13, 2001·Dementia and Geriatric Cognitive Disorders·B ReglandC G Gottfries
Apr 26, 2002·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Konstantin PrassAndreas Meisel
Sep 6, 2002·Journal of Alzheimer's Disease : JAD·Xue-Qing ChenWilliam H. Frey II
Jun 3, 2004·Annals of Neurology·Fabrizio TrincheseOttavio Arancio
Aug 4, 2004·Psychoneuroendocrinology·Christian BenedictWerner Kern
May 27, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Joanna L JankowskyAlena V Savonenko
Nov 25, 2005·Current Drug Delivery·Tushar K VyasAmbikanandan Misra
May 3, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Piotr HadaczekKrystof Bankiewicz
May 30, 2006·Neurobiology of Aging·David A CostaHuntington Potter
Jan 11, 2007·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Stephanie SchäferThomas A Bayer
Mar 10, 2007·Neurobiology of Aging·Maria Noêmia Martins de LimaNadja Schröder
May 4, 2007·International Journal of Pharmaceutics·Henry R CostantinoSteven C Quay
Jul 24, 2007·Neuroendocrinology·Christian BenedictWerner Kern
Feb 7, 2008·The Cochrane Database of Systematic Reviews·E SampsonR McShane
Feb 14, 2008·The Journal of Pharmacology and Experimental Therapeutics·Naoko NonakaWilliam A Banks
Oct 28, 2008·Journal of Alzheimer's Disease : JAD·Ashley I Bush
Apr 24, 2009·Journal of Alzheimer's Disease : JAD·Sandro Altamura, Martina U Muckenthaler
Jun 11, 2009·The Journal of Pharmacology and Experimental Therapeutics·Leah R HansonS Scott Panter
Oct 31, 2009·Journal of Pharmaceutical Sciences·Shyeilla V DhuriaWilliam H Frey
Dec 2, 2009·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Wei-Chih KanHsien-Yi Wang

❮ Previous
Next ❯

Citations

Apr 24, 2013·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Shailendra Kapoor
Jan 9, 2014·ASN Neuro·Kelsey J WeigelSteven M Levine
Jan 11, 2014·Journal of Drug Targeting·Sumeet SoodK Gowthamarajan
Jan 12, 2019·British Journal of Pharmacology·Sara NiksereshtScott Ayton
Jan 4, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Bhavani KashyapWilliam H Frey Ii
Oct 28, 2019·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Karla AcevedoAshley I Bush
Mar 20, 2015·Drug Delivery and Translational Research·Elizabeth JoachimHyungsoo Choi
Oct 29, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Andrew Gleason, Ashley I Bush
Jan 31, 2021·Pharmaceuticals·Jacob KosyakovskyLeah R Hanson
Oct 2, 2019·ACS Chemical Neuroscience·Jacob KosyakovskyJared M Fine

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Alzheimer's Disease: Animal Models

Alzheimer's disease is a neurodegenerative disease which can be studied using various experimental systems. This feed focuses on animal models used for Alzheimer's disease research.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.