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

• Published in: Drug delivery and translational research Vol. 2; no. 3; pp. 160 - 168
• Main Authors: Hanson, Leah R., Fine, Jared M., Renner, Dan B., Svitak, Aleta L., Burns, Rachel B., Nguyen, Thuhien M., Tuttle, Nathan J., Marti, Dianne L., Panter, S. Scott, Frey, William H.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-06-2012
• Subjects: Biomedical and Life Sciences; Biomedicine; Pharmaceutical Sciences/Technology; Research Article; Drug targeting; Iron; Amyloid; Morris water maze; Alzheimer’s disease; Metals
• ISSN: 2190-393X; 2190-3948
• DOI: 10.1007/s13346-011-0050-2

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
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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.