Nanoemulsions and nanocapsules as carriers for the development of intranasal mRNA vaccines

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. Consequently, we identified two promising candidates for nasal administration. These candidates include an NE incorporating a combination of an ionizable lipid (C12-200) and cationic lipid (DOTAP) for mRNA entrapment, along with DOPE to facilitate endosomal escape. This NE exhibited a size of 120 nm and a highly positive surface charge (+50 mV). Additionally, an NC formulation comprising the same components with a dextran sulfate shell was identified, with 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 NEs and NCs, robust antigen-specific CD8+ T cell responses were observed. These findings underscore the potential of NEs and polymeric NCs in advancing mRNA vaccine development for combating infectious diseases.