The aim of this innovative project is to develop and validate the biological efficacy of new formulations including original and patented reactivators (CNRS/IRBA). These molecules present a large spectrum of action against acetylcholinesterase (AChE) inhibited by Organophosphorus Neurotoxins (NOPs), hence the interest in developing centrally effective antidotes for nose-to-brain administration. The novel bilosome-based formulations designed at CEA will be administered via the non-invasive nasal route, which could enable delivery to the brain either after passage into the systemic circulation, or by absorption through the olfactory nerves which provides direct access to cerebrospinal fluid and brain parenchyma, bypassing the blood-brain barrier (BBB). The approval by health authorities of Nyxoïd (naloxone) and Valtoco (diazepam) demonstrates the relevance of nasal therapeutic approaches to emergency situations (e.g. overdose, epilepsy) in subjects who may be unconscious or in respiratory distress. The project's innovations could ultimately interest the recently-created french company OPGS Pharmaceuticals, for the valorization of the work with the preclinical development (toxicity, selectivity...) and a possible industrialization of this medical countermeasures.
The thesis will take place in TOULOUSE.