The lack of effective therapies mandates the development of new treatment strategies for ischemic stroke. The NR2B9c peptide can prevent N-Methyl-D-aspartate receptor (NMDAR)-mediated neurotoxicity induced by ischemia without affecting essential NMDAR activity and brings hope for stroke therapy. However, it is very difficult for NR2B9c to cross by itself the blood-brain barrier (BBB) and the neuron membrane. To provide a suitable delivery for unleashing the therapeutic potential of NR2B9c, in consideration of a high affinity of wheat germ agglutinin (WGA) for WGA receptors abundantly present on olfactory epithelium and neuronal surface, we developed WGA-modified nanoparticles carrying NR2B9c (NR2B9c-WGA-NPs). Following intranasal administration, NR2B9c-WGA-NPs are able to bypass the BBB and effectively transport NR2B9c into the brain and neuron, and therefore can protect neurons against excitotoxicity, reduce ischemic brain injury in rats and ameliorate their neurological function deficits. The intranasal administration of NR2B9c-WGA-NPs may serve as a practical stroke therapy.
Keywords: Ischemic stroke; NR2B9c; Nanoparticles; Nose to brain delivery; Wheat germ agglutinin.
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