Nose-to-brain delivery of nanomedicines to stimulate remyelination in the scope of multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) with no curative treatment. It is characterized by neuro-inflammation and demyelination within the CNS. In this context, we have selected prostaglandin D2 glycerol ester (PGD2-G), a potent anti-inflammatory bioactive lipid, and calcitriol, the active form of vitamin D capable of stimulating oligodendrocyte differentiation (the CNS-resident cells responsible for myelin production), to target neuro-inflammation and demyelination, respectively. To increase the therapeutic effects in the CNS, TAT-coated lipid nanocapsules (LNC) were used as a vehicle to protect the selected molecules from enzymatic degradation and increase their solubility in biological fluids. However, access to the CNS is limited by the blood-brain-barrier. Our strategy was to use the nose-to-brain delivery route as it enables direct transport from the nasal cavity to the brain. The aim of this work was to assess the capacity of the combination of the two nanoparticle formulations, to reduce neuro-inflammation and promote remyelination in MS-relevant animal models, following nasal administration.