Targeted nanomedicines to stimulate the differentiation of oligodendrocyte progenitor cells in the scope of multiple sclerosis
(2022)
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- Abstract
- Multiple sclerosis is an auto-immune disease caused by the destruction of the myelin sheath formed by oligodendrocytes in the central nervous system. Following myelin damage, a large panel of symptoms can appear, such as fatigue and gait problems. Remyelination is an endogenous process that allows myelin sheath regeneration with new oligodendrocytes. Those oligodendrocytes are generated by the differentiation of oligodendrocyte progenitor cells (OPC). We hypothesized that optimizing the delivery of drugs of interest to OPC could enhance their therapeutical effect. Thus, in this work we aimed to develop lipid nanocapsules (LNC) that could carry pro-remyelinating compounds selectively to OPC and favor their differentiation into oligodendrocytes. To do so, we grafted an antibody that targets PDGFRα, a receptor mainly expressed at the surface of OPC in the central nervous system. We found that the grafting of the anti-PDGFRα at LNC surface had an impact on their association with OPC. In parallel, we also investigated the possibility of delivering proremyelinating lipophilic compounds, via the nose-to-brain route. As lipophilic molecules can be challenging to administer to patients due to their low solubility in physiological solutions, we investigated the possibility of developing drug-loaded LNC formulations to facilitate their administration. Therefore, we encapsulated in LNC, retinoic acid, and calcitriol, two pro-remyelinating lipophilic molecules, and evaluated their impact on OPC differentiation in vitro and in vivo.
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Citations
Labrak, Y. (2022). Targeted nanomedicines to stimulate the differentiation of oligodendrocyte progenitor cells in the scope of multiple sclerosis. https://hdl.handle.net/2078.5/242523