RT Journal Article T1 Nanoemulsions and nanocapsules as carriers for the development of intranasal mRNA vaccines A1 López Borrajo, Mireya A1 Lou, Gustavo A1 Anthiya, Shubaash A1 Lapuhs, Philipp A1 Moreira Álvarez, David A1 Tobío Ageitos, Araceli A1 Loza García, María Isabel A1 Vidal Figueroa, Anxo A1 Alonso Fernández, María José K1 mRNA vaccine K1 Nanoparticles K1 Polymeric nanocapsule K1 SARS-CoV-2 K1 Intranasal vaccination AB The global emergency of coronavirus disease 2019 (COVID-19) has spurred extensive worldwide efforts to develop vaccines for protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our contribution to this global endeavor involved the development of a diverse library of nanocarriers, as alternatives to lipid nanoparticles (LNPs), including nanoemulsions (NEs) and nanocapsules (NCs), with the aim of protecting and delivering messenger ribonucleic acid (mRNA) for nasal vaccination purposes. A wide range of prototypes underwent rigorous screening through a series of in vitro and in vivo experiments, encompassing assessments of cellular transfection, cytotoxicity, and intramuscular administration of a model mRNA for protein translation. As a result, two promising candidates were identified for nasal administration. One of them was a NE incorporating a combination of an ionizable lipid (C12-200) and cationic lipid (DOTAP), both intended to condense mRNA, along with DOPE, which is known to facilitate endosomal escape. This NE exhibited a size of 120 nm and a highly positive surface charge (+ 50 mV). Another candidate was an NC formulation comprising the same components and endowed with a dextran sulfate shell. This formulation showed a size of 130 nm and a moderate negative surface charge (-16 mV). Upon intranasal administration of mRNA encoding for ovalbumin (mOVA) associated with optimized versions of the said NE and NCs, a robust antigen-specific CD8 + T cell response was observed. These findings underscore the potential of NEs and polymeric NCs in advancing mRNA vaccine development for combating infectious diseases. PB Springer SN 2190-3948 YR 2024 FD 2024-05-29 LK http://hdl.handle.net/10347/34450 UL http://hdl.handle.net/10347/34450 LA eng NO Borrajo, M.L., Lou, G., Anthiya, S. et al. Nanoemulsions and nanocapsules as carriers for the development of intranasal mRNA vaccines. Drug Deliv. and Transl. Res. 14, 2046–2061 (2024). https://doi.org/10.1007/s13346-024-01635-5 NO This work was supported by Instituto de SaludCarlos III project “COVARNA”, under grant agreement COV20-00214, and by the Competitive Reference Groups, Consellería de Educacióne Ordenación Universitaria, Xunta de Galicia. Ref: ED431C2017/09. Mireya L. Borrajo acknowledges the financial support byInstituto de Salud Carlos III through the “Contratos i-PFIS: DoctoradosISS-empresa en Ciencias y Tecnologías de la Salud” (IFI19/00033).The authors want to acknowledge Daniel Beiroa Tarrío for his work atthe animal facility, and Iria Gómez Touriño for her availability in theuse of Mabtech® ELISpot reader. Graphical abstract was created withBioRender.com.Funding Open Access funding provided thanks to the CRUE-CSICagreement with Springer Nature. DS Minerva RD 28 abr 2026