DOWNALZ

This project aims at designing novel pleiotropic prodrugs, under a mucoadhesive liposomal formulation for intranasal administration, with potential therapeutic interest in Down Syndrome (DS) and Alzheimer's disease (AD). The prodrugs will be activated through the covalent inhibition of butyrylcholinesterase (BuChE), able to counteract the cholinergic neurodegeneration in AD. The released drugs will then target either the beta2-A or 5-HT4 receptors or the pro-neuroinflammatory HMGB1 protein, in order to display a potential additional neuroprotective effect. The liposomal formulation and the intranasal administration will enhance the CNS distribution of the prodrugs for a selective activation by the cerebral BuChE, in order to improve the central effects of the released drugs and potentially avoid their peripheral side effects.