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Squalenoyl adenosine nanoparticles provide neuroprotection after stroke and spinal cord injury
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Squalenoyl adenosine nanoparticles provide neuroprotection after stroke and spinal cord injury
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Journal Article
Squalenoyl adenosine nanoparticles provide neuroprotection after stroke and spinal cord injury
2014
Overview
There is an urgent need to develop new therapeutic approaches for the treatment of severe neurological trauma, such as stroke and spinal cord injuries. However, many drugs with potential neuropharmacological activity, such as adenosine, are inefficient upon systemic administration because of their fast metabolization and rapid clearance from the bloodstream. Here, we show that conjugation of adenosine to the lipid squalene and the subsequent formation of nanoassemblies allows prolonged circulation of this nucleoside, providing neuroprotection in mouse stroke and rat spinal cord injury models. The animals receiving systemic administration of squalenoyl adenosine nanoassemblies showed a significant improvement of their neurologic deficit score in the case of cerebral ischaemia, and an early motor recovery of the hindlimbs in the case of spinal cord injury. Moreover,
in vitro
and
in vivo
studies demonstrated that the nanoassemblies were able to extend adenosine circulation and its interaction with the neurovascular unit. This Article shows, for the first time, that a hydrophilic and rapidly metabolized molecule such as adenosine may become pharmacologically efficient owing to a single conjugation with the lipid squalene.
The systemic circulation time of adenosine is prolonged by forming nanoassemblies with squalene, and this can improve neurologic recovery in mice affected by a stroke or spinal cord injury.
Publisher
Nature Publishing Group UK,Nature Publishing Group
