Squalenoyl adenosine nanoparticles provide neuroprotection after stroke and spinal cord injury View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-12

AUTHORS

Alice Gaudin, Müge Yemisci, Hakan Eroglu, Sinda Lepetre-Mouelhi, Omer Faruk Turkoglu, Buket Dönmez-Demir, Seçil Caban, Mustafa Fevzi Sargon, Sébastien Garcia-Argote, Grégory Pieters, Olivier Loreau, Bernard Rousseau, Oya Tagit, Niko Hildebrandt, Yannick Le Dantec, Julie Mougin, Sabrina Valetti, Hélène Chacun, Valérie Nicolas, Didier Desmaële, Karine Andrieux, Yilmaz Capan, Turgay Dalkara, Patrick Couvreur

ABSTRACT

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. More... »

PAGES

1054-1062

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nnano.2014.274

DOI

http://dx.doi.org/10.1038/nnano.2014.274

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1051588906

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25420034


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