Deferoxamine (DFO) is a high-affinity iron chelator approved by the Food
and Drug Administration for treating iron overload. Preclinical research
suggests that systemically administered DFO prevents and treats ischemic
stroke damage and intracerebral hemorrhage. However, translation into human
trials has been limited, probably because of difficulties with DFO
administration. A noninvasive method of intranasal administration has emerged
recently as a rapid way to bypass the blood-brain barrier and target
therapeutic agents to the central nervous system. We report here that
intranasal administration targets DFO to the brain and reduces systemic
exposure, and that intranasal DFO prevents and treats stroke damage after
middle cerebral artery occlusion (MCAO) in rats. A 6-mg dose of DFO resulted
in significantly higher DFO concentrations in the brain (0.9–18.5 μM)
at 30 min after intranasal administration than after intravenous
administration (0.1–0.5 μM, p < 0.05). Relative to blood
concentration, intranasal delivery increased targeting of DFO to the cortex
approximately 200-fold compared with intravenous delivery. Intranasal
administration of three 6-mg doses of DFO did not result in clinically
significant changes in blood pressure or heart rate. Pretreatment with
intranasal DFO (three 6-mg doses) 48 h before MCAO significantly decreased
infarct volume by 55% versus control (p < 0.05). In addition,
post-treatment with intranasal administration of DFO (six 6-mg doses)
immediately after reperfusion significantly decreased infarct volume by 55%
(p < 0.05). These experiments suggest that intranasally
administered DFO may be a useful treatment for stroke, and a prophylactic for
patients at high risk for stroke