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Delivery of Therapeutic siRNA to the CNS Using Cationic and Anionic Liposomes
Published on: July 23, 2016
Ionizable nanoemulsions for RNA delivery into the central nervous system - importance of diffusivity
Mireya L Borrajo1, Aloia Quijano2, Philipp Lapuhs1
1Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Av. Barcelona s/n, Campus Vida, University de Santiago de Compostela, 15782 Santiago de Compostela, Spain; Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; IDIS Research Institute, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Abstract:
Lipid nanoparticles (LNPs) currently dominate the RNA delivery landscape; however their limited diffusivity hampers targeted tissue dissemination, and, hence, their capacity for intracellular drug delivery. This is especially relevant for tissues such as the central nervous system (CNS), where overcoming proactive brain barriers is crucial for the efficacy of genetic therapeutics. This research aimed to create ionizable nanoemulsions (iNEs), a new generation of RNA delivery systems with enhanced diffusivity. The developed iNEs (consisting of the combination of C12-200, DOPE, Vitamin E, and DMG-PEG) with a size below 100 nm, neutral surface charge, and high RNA loading capacity, showed excellent cell viability and transfection efficiency in various cellular models, including neurons, astrocytes, and microglia. Subsequently, iNEs containing mRNA GFP were tested for CNS transfection, highlighting their exceptional diffusivity and selective transfection of neurons following intra-parenchymal administration.
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