RT Journal Article
T1 Ionizable nanoemulsions for RNA delivery into the central nervous system – importance of diffusivity
A1 López Borrajo, Mireya
A1 Quijano Ocampo, Aloia
A1 Lapuhs, Philipp
A1 Rodríguez Pérez, Ana Isabel
A1 Anthiya, Shubaash
A1 Labandeira García, José Luis
A1 Valenzuela Limiñana, Rita
A1 Alonso Fernández, María Josefa
K1 Brain delivery
K1 Diffusivity
K1 mRNA
K1 Nanoemulsion
K1 RNA therapeutics
K1 siRNA
AB 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
PB Elsevier
SN 0168-3659
YR 2024
FD 2024-06-24
LK http://hdl.handle.net/10347/34892
UL http://hdl.handle.net/10347/34892
LA eng
NO Journal of Controlled Release 372 (2024) 295-303
NO This work was supported by B-SMART project, funded by the European Union's Horizon 2020 research and innovation program under grant agreement No 721058. Authors also acknowledge the Competitive Reference Groups, Consellería de Educación e Ordenación Universitaria, Xunta de Galicia (Ref. ED431C 2021/17 and ED431C 22/41). Financial support from the Xunta de Galicia (Centro singular de Investigación de Galicia accreditation 2019-2022), the (European Union European Regional Development Fund – ERDF), and the Spanish Ministry of Science and Innovation (PID2021-126848NB-100) are gratefully acknowledged. Mireya L. Borrajo acknowledges the financial support by Instituto de Salud Carlos III through the “Contratos i-PFIS: Doctorados ISS-empresa en Ciencias y Tecnologías de la Salud” (IFI19/00033)
DS Minerva
RD 4 may 2026