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[Display omitted] Effective vaccines delivered via painless methods would revolutionize the way people approach vaccinations. This study focused on the development of fast-dissolving microneedles (MNs) to deliver antigen-loaded sustained release polymeric nanoparticles (NPs), achieving a dual-delivery platform for vaccination through the skin. The platform utilizes dissolving MNs (dMNs), which penetrate to the epidermal layer of the skin and rapidly dissolve, releasing the antigen-loaded NPs. In this study, seven dissolving microneedle formulations were tested based on screening of various biocompatible and biodegradable polymers and sugars. The lead dMN formulation was selected based on optimal mechanical strength and dissolution of the needles and was loaded with poly(lactic-co-glycolic) acid (PLGA) NPs encapsulating a model influenza matrix 2 (M2) protein antigen. Antigen-loading efficiency in the needles was determined by centrifugation of the lead formulation containing various concentrations of antigen nanoparticles. Next, the reproducibility and translatability of ex vivo mechanical strength and dissolvability of the lead M2 PLGA NP-loaded dMN formulation was assessed by formulating and testing two different microneedle arrays on murine and porcine skin. Finally, the lead microneedle array was loaded with fluorescent dye NPs and evaluated for pore formation and closure in vivo in a murine model. This proof-of-concept study yielded an easy-to-formulate, well-characterized, translatable antigen NP-loaded dMN platform for transdermal vaccine administration. [ABSTRACT FROM AUTHOR]