Development and Evaluation of an Oral mRNA Vaccine Delivery Platform: From Injectable Nanoparticles to Gastrointestinal-Protective Capsules

Abstract

Messenger RNA (mRNA) vaccines have transformed modern vaccinology by allowing cells to produce antigenic proteins directly from transient genetic instructions. Despite their rapid development and strong immunogenic potential, conventional mRNA vaccines are predominantly administered by injection, creating practical limitations related to needle use, trained personnel, cold-chain requirements, and repeated-dose administration. Oral delivery could provide a more convenient and potentially scalable alternative, but mRNA molecules are highly vulnerable to degradation within the gastrointestinal tract. This study proposes the development and evaluation of an oral mRNA vaccine delivery platform designed to protect mRNA during gastric transit and promote controlled release and cellular uptake in the intestine. The proposed formulation combines mRNA-loaded nanoparticles with an enteric-protective capsule or coating designed to respond to gastrointestinal pH. The research framework includes physicochemical characterization, mRNA integrity assessment, simulated gastrointestinal stability testing, release profiling, cellular uptake, protein-expression analysis, and evaluation of vaccine-induced immune responses in an appropriate preclinical model. Key formulation variables include particle size, polydispersity, surface charge, encapsulation efficiency, mRNA integrity, release behavior, and biological activity. Statistical analysis should compare the oral formulation with an injectable mRNA formulation and appropriate controls using validated parametric or non-parametric methods according to data distribution. Previous research has demonstrated the feasibility of gastrointestinal mRNA vaccination, but important challenges remain in formulation stability, intestinal delivery, reproducibility, storage, and translational scalability. The proposed platform therefore focuses on improving the practical performance of oral mRNA vaccination rather than simply changing the administration route. A successful formulation could contribute to the development of needle-free, self-administered, and potentially more accessible mRNA vaccination technologies.